Affinage

Showing PTK2B — PYK2 is a alias.

PTK2B

Protein-tyrosine kinase 2-beta · UniProt Q14289

Length
1009 aa
Mass
115.9 kDa
Annotated
2026-06-10
100 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTK2B (PYK2/RAFTK/CADTK) is a calcium-sensitive, non-receptor tyrosine kinase of the FAK family that couples diverse extracellular stimuli to cytoskeletal remodeling, MAP kinase cascades, and immune signaling (PMID:7499242, PMID:8695788, PMID:8670418). Its activation is gated by intracellular Ca2+: the disordered kinase-FAT linker contains a calmodulin-binding element whose Ca2+-promoted engagement of CaM drives fuzzy dimerization and intermolecular (trans) autophosphorylation specifically at Tyr402, a step that is Src-independent but creates the Src-binding site that amplifies downstream substrate phosphorylation (PMID:15166227, PMID:35945264). Once activated, PYK2 nucleates signaling complexes by recruiting Src-family kinases, Grb2, and paxillin through its phospho-Tyr and proline-rich/C-terminal domains (PMID:8695788, PMID:9091579, PMID:9560226), and functions both as a kinase and as a scaffold linking integrin, GPCR, growth factor, and stress inputs to JNK, ERK/Ras, and p38 MAPK pathways (PMID:8670418, PMID:9120025, PMID:9774361, PMID:14676843). PYK2 directly phosphorylates a broad substrate range—the Kv1.2 potassium channel, GSK3β at Tyr216 to activate Wnt/β-catenin signaling and intestinal tumorigenesis, cortactin at invadopodia to promote ECM degradation and invasion, connexin-43 to suppress gap-junction communication, and the antiviral kinase TBK1 at Tyr591 to drive its oligomerization and innate immune signaling (PMID:9560226, PMID:26274564, PMID:29133485, PMID:32956670, PMID:37989995). It activates the small GTPase RhoA via PDZ-RhoGEF and Graf1, linking Ca2+ to actin dynamics and synapse maintenance (PMID:19759375, PMID:30626696), and operates in macrophage inflammatory signaling through MyD88 and IRF5 (PMID:19955209, PMID:34795257). PYK2 activity is negatively regulated by the phosphatase STEP, which dephosphorylates Tyr402, by FIP200 binding the kinase domain, and by protocadherins and SIRPα, and is positively organized by PSD-95-mediated postsynaptic clustering downstream of NMDA-receptor Ca2+ influx, where it is required for hippocampal LTP (PMID:10769033, PMID:20071509, PMID:22544749, PMID:19047047, PMID:36202053). In the brain it phosphorylates tau and contributes to synaptic and tauopathy phenotypes (PMID:29782321, PMID:35501917). Beyond kinase signaling, PYK2 controls cell migration, spreading, apoptosis, and cell-cycle progression in a manner distinct from FAK and mapped to its N- and C-terminal domains (PMID:10934044, PMID:11062241, PMID:15967096).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1995 Medium

    Establishing that a FAK-related cytoplasmic tyrosine kinase exists outside focal-adhesion receptors answered whether non-integrin stimuli could engage a FAK-like kinase, defining PYK2 as a distinct cytoplasmic enzyme.

    Evidence cDNA cloning and sequence analysis with thrombin-induced phosphorylation in megakaryocytic cells

    PMID:7499242

    Open questions at the time
    • No structural basis for activation defined
    • Substrates and downstream pathways unidentified
  2. 1996 High

    Showing intrinsic kinase/autokinase activity, fibronectin-induced focal-adhesion localization, and SH2-mediated recruitment of Src, Fyn, and Grb2 established PYK2 as an integrin-responsive scaffold that recruits Src-family kinases.

    Evidence In vitro kinase assay, reciprocal Co-IP, and confocal localization in megakaryocytic and COS cells

    PMID:8695788

    Open questions at the time
    • Autophosphorylation site not defined
    • Direct substrates not identified
  3. 1996 High

    Placing PYK2 upstream of JNK in response to TNF-alpha, UV, and osmotic shock connected the kinase to stress-activated signaling, extending its role beyond adhesion.

    Evidence Overexpression and dominant-negative epistasis with JNK activity readout

    PMID:8670418

    Open questions at the time
    • Intermediate signaling components to JNK not resolved
    • Direct vs scaffold contribution unclear
  4. 1997 Medium

    Identifying Ca2+/PKC-dependent, calpain-regulated activation in platelets and TCR-stimulated T cells answered how surface-receptor signals feed into PYK2, linking it to calcium and cytoskeletal integrity across cell types.

    Evidence Platelet and T-cell activation assays, pharmacological dissection, SH2-domain binding and Co-IP

    PMID:9091579 PMID:9099753

    Open questions at the time
    • Molecular Ca2+ sensor not yet defined
    • Functional consequences of partner recruitment incomplete
  5. 1998 High

    Demonstrating GPCR-coupled activation (muscarinic, CCR5, angiotensin II) with substrate phosphorylation of Kv1.2 and downstream Ras/ERK, JNK and p38 established PYK2 as a hub bridging GPCR signaling to ion channels and MAPK cascades.

    Evidence Stable cell lines, site-directed mutagenesis of phospho-tyrosines, in vitro phosphorylation, dominant-negative epistasis, Ras-GTP/ERK assays

    PMID:9446638 PMID:9560226 PMID:9774361

    Open questions at the time
    • Direct receptor-PYK2 coupling mechanism not defined
    • Generality of Kv1.2 phosphorylation in vivo untested
  6. 1999 Medium

    Linking PYK2 kinase activity to dexamethasone-induced apoptosis in myeloma cells assigned the kinase a pro-apoptotic role in a defined, stimulus-specific death pathway.

    Evidence Transient overexpression and kinase-inactive mutant in apoptosis assays

    PMID:10597281

    Open questions at the time
    • Apoptotic effector mechanism downstream of PYK2 not defined
    • Cell-type generality unknown
  7. 2000 High

    Identifying FIP200 as a direct kinase-domain inhibitor that dissociates upon stimulation provided the first negative-regulatory mechanism for PYK2.

    Evidence Yeast two-hybrid, in vitro binding and kinase-inhibition assays, Co-IP in SYF cells

    PMID:10769033

    Open questions at the time
    • Structural basis of FIP200-mediated inhibition not resolved
    • Stimulus-induced dissociation trigger unknown
  8. 2000 High

    Defining domain-specific control of migration, spreading, cell-cycle, and neurite outgrowth—distinct from FAK and mapped to N- and C-terminal domains—established PYK2's non-redundant cellular roles.

    Evidence Chimeric/domain-deletion constructs, dominant-negative CRNK, motility and flow-cytometry assays in monocytes, PC12, and fibroblasts

    PMID:10934044 PMID:10980697 PMID:11062241

    Open questions at the time
    • Effectors mediating C-terminal cell-cycle inhibition not identified
    • Mechanism of cytoplasmic vs focal-adhesion localization difference unclear
  9. 2001 Medium

    Identifying nephrocystin-mediated recruitment to cell-matrix adhesions and PI3K/SHP-2 association in platelets clarified how PYK2 is positioned at adhesion complexes and its Tyr402 activation triggered.

    Evidence Co-IP of endogenous complexes, phospho-Y402 Western blot, pharmacological PI3K epistasis, ERK and angiogenesis assays

    PMID:11472358 PMID:11493697 PMID:11739395

    Open questions at the time
    • Direct vs indirect nature of partner interactions not fully resolved
    • In vivo relevance of complexes untested
  10. 2002 Medium

    Establishing PYK2 as a Src-coordinating scaffold phosphorylating p190RhoGAP, PDK1, ARA55, and alpha-synuclein, and as a driver of breast-cancer invasion and cardiomyocyte apoptosis, broadened its substrate repertoire and showed Tyr402 is required for these outputs.

    Evidence Site-directed mutagenesis (Y402, PDK1-Y9), Co-IP, in vitro phosphorylation, invasion and apoptosis assays

    PMID:10713673 PMID:11856738 PMID:12096713 PMID:15322113

    Open questions at the time
    • Direct vs Src-relayed phosphorylation of each substrate not always separated
    • Physiological substrate set incomplete
  11. 2003 Medium

    Demonstrating PYK2 scaffolds Src-dependent PDK1 phosphorylation at focal adhesions integrated PYK2 into adhesion-coupled signaling downstream of angiotensin II.

    Evidence Adenoviral expression, PDK1-Y9 mutagenesis, confocal co-localization, Co-IP in vascular smooth muscle

    PMID:14585963

    Open questions at the time
    • Downstream PDK1 effector outputs not mapped
    • Generality beyond VSMC unknown
  12. 2004 High

    Establishing that autophosphorylation occurs in trans, only at Tyr402, and is Src-independent answered the long-standing mechanism of PYK2 activation and defined the order: trans-autophosphorylation precedes Src recruitment and substrate amplification.

    Evidence Dual-tag constructs, affinity chromatography, in vitro kinase assays in SYF cells, plus VEGF-dependent Ca2+-sensitive p38 pathway dissection

    PMID:14676843 PMID:15166227

    Open questions at the time
    • Structural trigger for self-association not yet defined
    • Stoichiometry of active dimers unresolved
  13. 2005 Medium

    Mapping migration stimulation to the N-terminal domain and establishing junctional recruitment with beta-catenin phosphorylation and SAPAP3/PSD-95 anchoring connected PYK2 to barrier function, glioma migration, and postsynaptic positioning.

    Evidence Domain-swap chimeras, siRNA knockdown/rescue, dominant-negative CRNK, junctional imaging, yeast two-hybrid and PSD fractionation

    PMID:15778498 PMID:15967096 PMID:16202977

    Open questions at the time
    • N-terminal effectors driving migration unidentified
    • Direct vs scaffold role at junctions not fully separated
  14. 2008 Medium

    Showing protocadherin binding inhibits PYK2 and that PYK2 is hyperactive in Pcdh-deficient neurons added a developmental, neuron-specific layer of negative regulation.

    Evidence Co-IP, kinase assays in Pcdh-gamma-null neurons, overexpression in chick spinal cord

    PMID:19047047

    Open questions at the time
    • Structural basis of protocadherin-mediated inhibition unknown
    • Direct vs complex-mediated effect not resolved
  15. 2009 Medium

    Defining the PYK2/PDZ-RhoGEF/RhoA axis and the MyD88 interaction established how PYK2 converts Ca2+ signals to RhoA activation and links it to innate NF-κB inflammatory signaling.

    Evidence In vitro phosphorylation/activation, knockdown epistasis, RhoA assays, Co-IP with death-domain mapping in macrophages

    PMID:19759375 PMID:19955209

    Open questions at the time
    • Direct PYK2-MyD88 phosphorylation event not defined
    • PDZ-RhoGEF phospho-site not mapped
  16. 2010 High

    Demonstrating PSD-95-driven postsynaptic clustering and Ca2+/CaM-dependent Tyr402 autophosphorylation required for hippocampal LTP, plus mGluR scaffolding, established PYK2 as a key effector of NMDA-receptor calcium signaling in synaptic plasticity.

    Evidence Overexpression, in vitro oligomerization, calcium imaging, LTP electrophysiology, brain Co-IP and GST pull-down

    PMID:20071509 PMID:20180987

    Open questions at the time
    • Synaptic substrates mediating LTP not fully defined
    • Quantitative link between clustering and kinase output incomplete
  17. 2012 High

    Identifying STEP as a phosphatase that dephosphorylates Tyr402 and blocks postsynaptic translocation defined a key physiological off-switch opposing depolarization-induced PYK2 activation.

    Evidence In vitro phosphatase assay, Co-IP, STEP KO mice with paxillin/ASAP1 substrate readouts and fractionation

    PMID:22544749

    Open questions at the time
    • Regulation of STEP-PYK2 engagement not defined
    • Other phosphatases not excluded
  18. 2015 High

    Establishing GSK3β-Y216 as a direct substrate driving Wnt/β-catenin signaling and intestinal tumorigenesis, plus EGFR-endosomal STAT3 feedback and astrocyte migration roles, connected PYK2 to oncogenic transcriptional programs and tissue repair.

    Evidence In vitro kinase assay, mutagenesis, APCmin/+ mouse model with pharmacological inhibition, ChIP, knockout astrocytes

    PMID:25648557 PMID:26274564 PMID:26663135

    Open questions at the time
    • In vivo relevance of STAT3 feedback loop untested
    • Gelsolin recruitment mechanism in astrocytes incomplete
  19. 2017 High

    Identifying cortactin as a direct invadopodial substrate distinguished PYK2 from FAK by assigning it control of invadopodium-mediated ECM degradation and invasion.

    Evidence Protein-array substrate screening, in vitro kinase assay, Co-IP, siRNA knockdown/rescue, invasion assays

    PMID:29133485

    Open questions at the time
    • Relative contribution of direct vs Arg-mediated cortactin phosphorylation not quantified
    • In vivo metastasis relevance untested
  20. 2018 Medium

    Placing PYK2 downstream of Fyn as a direct tau kinase and within a Pcdha/WAVE/Rac1 neuronal migration axis extended its substrate range into neurodegeneration-relevant and developmental pathways.

    Evidence In vitro kinase assays, Co-IP, FynCA/FynKO and Pcdha-cluster knockout mice, Rac1 activity and migration assays

    PMID:29782321 PMID:29911975

    Open questions at the time
    • Tau phosphosites and pathological consequence in vivo not fully resolved at this stage
    • Mechanism of Rac1 inactivation by PYK2 unclear
  21. 2018 Medium

    Identifying PYK2 as a positive regulator of TAZ/YAP stability in triple-negative breast cancer assigned a FAK-independent role in Hippo-pathway transcriptional output.

    Evidence siRNA knockdown, kinase inhibitor with FAK-specificity control, proteasomal-degradation and reporter assays

    PMID:30250159

    Open questions at the time
    • Direct TAZ/LATS phosphosites not mapped
    • In vivo tumor relevance untested
  22. 2019 Medium

    Defining a PYK2/Graf1/RhoA pathway required for amyloid-beta-induced spine loss linked PYK2 RhoGAP inhibition to synapse maintenance in neurodegeneration.

    Evidence Brain biochemical isolation, Co-IP, kinase assay, dendritic-spine imaging and RhoA activity assay

    PMID:30626696

    Open questions at the time
    • Graf1 phosphosite not identified
    • Direct vs indirect inhibition of Graf1c unresolved
  23. 2020 High

    Mapping connexin-43 phosphosites and the CD56-PYK2 axis in NK cells connected PYK2 to gap-junction communication and immune-synapse-driven cytotoxic granule exocytosis.

    Evidence In vitro phosphorylation with mass spectrometry, GJIC dye-transfer assays, CRISPR CD56 knockout/rescue with cytotoxicity and synapse imaging

    PMID:32510326 PMID:32956670

    Open questions at the time
    • How CD56 couples to PYK2 Tyr402 phosphorylation not defined
    • Functional consequence of each Cx43 phosphosite not separated
  24. 2022 High

    Resolving that the disordered kinase-FAT linker binds calmodulin and that Ca2+ promotes CaM-induced fuzzy dimerization driving trans-autophosphorylation provided the structural mechanism for calcium-sensing activation, unifying decades of Ca2+-dependence observations.

    Evidence NMR spectroscopy, biophysical binding assays, mutagenesis of the KFL/FERM-kinase fragment

    PMID:35945264

    Open questions at the time
    • Full-length activated complex structure not determined
    • Quantitative coupling of dimer formation to cellular activity incomplete
  25. 2022 Medium

    Identifying SIRPα as a direct C-terminal inhibitor of PYK2 controlling macrophage necroptosis added a receptor-coupled negative-regulatory mechanism in myeloid homeostasis.

    Evidence Co-IP with domain mapping, PYK2 activity assay, SIRPα-null macrophages, necroptosis assay

    PMID:36202053

    Open questions at the time
    • Structural basis of inhibition not resolved
    • Downstream necroptosis effector pathway from PYK2 incomplete
  26. 2022 Medium

    Showing Pyk2 deletion worsens tauopathy by relieving its suppression of LKB1/p38 reframed PYK2 as a context-dependent suppressor of tau pathology, in apparent contrast to its direct tau-kinase activity.

    Evidence Conditional Pyk2 knockout in PS19 mice, proteomics, phospho-tau Western blot, LKB1/p38 activity assays, behavior

    PMID:35501917

    Open questions at the time
    • Reconciliation of direct tau phosphorylation with net protective role unresolved
    • Mechanism of LKB1/p38 suppression not defined
  27. 2023 High

    Establishing PYK2 as a direct TBK1-Y591 kinase that also drives STING oligomerization kinase-independently defined a non-redundant role in antiviral innate immunity, with knockout mice showing increased viral susceptibility.

    Evidence In vitro kinase assay, Co-IP, oligomerization assays, Ptk2b-/- mice and viral infection

    PMID:37989995

    Open questions at the time
    • Structural basis of kinase-independent STING oligomerization unclear
    • Upstream trigger for antiviral PYK2 activation not defined
  28. 2023 Medium

    Defining IRF5 as a direct PYK2 substrate and showing m6A/Mettl3/Ythdf2 control of Pyk2 mRNA stability connected the kinase to transcriptional control of macrophage inflammation and to post-transcriptional regulation of its own abundance.

    Evidence Kinase inhibitor library screen, PYK2-deficient macrophages, transcriptomics, colitis models, RIP-PCR and mRNA-stability assays

    PMID:34795257 PMID:37952687

    Open questions at the time
    • IRF5 phosphosites not mapped
    • Upstream signals controlling m6A-mediated Pyk2 regulation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many context-dependent and even opposing outputs of PYK2 (pro- vs anti-tumorigenic, pro- vs anti-tau-pathology, kinase-dependent vs scaffold roles) are selected within a single cell remains unresolved.
  • No unifying model of how stimulus identity dictates which PYK2 substrate/scaffold output dominates
  • Full-length structures of activated PYK2 complexes lacking
  • In vivo substrate hierarchy across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0060090 molecular adaptor activity 4 GO:0140299 molecular sensor activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 4 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3
Partners
FIP200FYNGRB2MYD88PTPN5PXNSIRPASRC
Complex memberships
postsynaptic density

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 RAFTK/PYK2 was identified as a novel cytoplasmic tyrosine kinase (1009 aa) related to FAK, lacking transmembrane regions, myristylation sites, and SH2/SH3 domains, but containing a kinase domain flanked by large N- and C-terminal domains with a proline-rich C-terminal stretch. It is expressed in megakaryocytes and brain, and thrombin stimulation of megakaryocytic CMK cells induced rapid tyrosine phosphorylation of the ~123-kDa RAFTK protein. cDNA cloning, sequence analysis, immunoprecipitation, Western blot The Journal of biological chemistry Medium 7499242
1996 RAFTK/PYK2 has intrinsic tyrosine kinase and autokinase activities. It localizes to focal adhesion-like structures (co-localizing with vinculin) upon fibronectin activation in megakaryocytic CMK cells and transfected COS cells. Its SH2 domains of Src, Fyn, and adaptor Grb2 associate specifically with tyrosine-phosphorylated RAFTK. Fibronectin-induced integrin signaling triggers RAFTK phosphorylation, and dephosphorylation occurs upon cell detachment with re-phosphorylation upon replating on fibronectin. In vitro kinase assay, immunoprecipitation, confocal microscopy, transfection of COS cells Blood High 8695788
1996 Pyk2 is activated by stress signals including TNF-alpha, UV irradiation, and osmotic shock, and overexpression of Pyk2 leads to JNK activation. A dominant-negative Pyk2 mutant interferes with UV- or osmotic shock-induced JNK activation, placing Pyk2 upstream of JNK in stress signaling. Overexpression, dominant-negative mutant, kinase activity assay Science High 8670418
1997 RAFTK is tyrosine-phosphorylated rapidly (within 10 s) during early platelet activation by thrombin in an integrin glycoprotein IIb-IIIa-independent manner. RAFTK phosphorylation is calcium-dependent, regulated by protein kinase C, requires intact actin cytoskeleton (blocked by cytochalasin D), and occurs independently of platelet aggregation. RAFTK is proteolytically cleaved by calpain in an aggregation-dependent manner. Platelet activation assays, immunoprecipitation, Western blot, pharmacological inhibitors The Journal of biological chemistry Medium 9099753
1997 RAFTK is phosphorylated and its kinase activity increases upon T cell receptor (TCR) activation in human T cells. After TCR stimulation, Fyn and Grb2 associate with phospho-RAFTK via their SH2 domains; RAFTK also co-immunoprecipitates with Lck SH2 domain and with paxillin via its C-terminal proline-rich domain. Cytochalasin D pretreatment reduces RAFTK phosphorylation, implicating cytoskeletal integrity in this process. Immunoprecipitation, kinase assay, SH2 domain binding, Western blot The Journal of experimental medicine Medium 9091579
1997 RAFTK activation in Kaposi's sarcoma cells by multiple cytokines (bFGF, VEGF, VRP, OSM, IL-6, TNF-alpha) leads to its association with paxillin via the hydrophobic C-terminal domain of the kinase, and downstream JNK activation. Immunoprecipitation, kinase assay, Western blot The Journal of clinical investigation Medium 9120025
1998 MIP-1β binding to CCR5 activates RAFTK, with subsequent activation of paxillin, JNK/SAPK, and p38 MAPK. A dominant-negative RAFTK kinase mutant markedly attenuates JNK/SAPK activity downstream of CCR5, placing RAFTK as a functional bridge linking CCR5 receptor signaling to the cytoskeleton and nucleus. Dominant-negative mutant, kinase assay, Western blot Blood Medium 9446638
1998 m1 muscarinic acetylcholine receptor activation stimulates PYK2 tyrosine kinase activity. Two specific tyrosine residues on PYK2 are phosphorylated upon muscarinic signaling, inducing binding of c-Src and Grb2 to PYK2. PYK2 specifically phosphorylates the C-terminal cytosolic portion of potassium channel Kv1.2 in an m1 receptor-regulated manner. Paxillin associates constitutively with PYK2 independent of muscarinic signaling. Stable cell lines, kinase assay, site-directed mutagenesis of phosphorylation sites, in vitro phosphorylation Proceedings of the National Academy of Sciences of the United States of America High 9560226
1998 In cardiac fibroblasts, angiotensin II activates Pyk2/CAKbeta/RAFTK in a Ca2+/calmodulin-sensitive manner. Overexpression of dominant-negative Pyk2 significantly attenuates Ang II- or calcium ionophore-induced ERK activities and GTP-Ras loading, placing Pyk2 upstream of the Ras/ERK pathway downstream of Ang II. Dominant-negative overexpression, ERK kinase assay, Ras-GTP loading assay, pharmacological inhibitors Hypertension Medium 9774361
1999 RAFTK/Pyk2 activation is required for dexamethasone-induced apoptosis in multiple myeloma cells. Wild-type RAFTK overexpression induces apoptosis, while kinase-inactive RAFTK blocks dexamethasone-induced apoptosis but not IR- or Fas-mediated apoptosis. IL-6 inhibits both RAFTK activation and dexamethasone-triggered apoptosis. Transient overexpression, kinase-inactive mutant, apoptosis assays Oncogene Medium 10597281
2000 Pyk2 and FAK associate with EGF receptor-containing adhesion complexes through their C- and N-terminal domains, respectively, during neurite outgrowth. Expression of the C-terminal domain of Pyk2 or FAK blocks neurite outgrowth but not ERK activation. Autophosphorylation of Pyk2/FAK and phosphorylation of paxillin are required for neurite formation. Overexpression of domain constructs, immunoprecipitation, morphological assay in PC12 and SH-SY5Y cells Nature cell biology Medium 10980697
2000 RAFTK/Pyk2 tyrosine phosphorylation upon NGF stimulation requires phospholipase Cγ activity and intracellular Ca2+. Paxillin co-immunoprecipitates with RAFTK and its phosphorylation is Ca2+-dependent. By confocal microscopy, RAFTK translocates from cytoplasm to neurite initiation sites at the cell periphery within 5 min, where it co-localizes with paxillin and actin. Potassium depolarization induces RAFTK and paxillin phosphorylation in a Ca2+-dependent manner. Immunoprecipitation, confocal microscopy, pharmacological inhibitors, Western blot The Journal of biological chemistry Medium 10764815
2000 FIP200 (FAK family kinase-interacting protein of 200 kDa) was identified as a Pyk2-interacting protein that binds the kinase domain of Pyk2 and inhibits its kinase activity in vitro. FIP200 inhibits Pyk2 kinase activity isolated from SYF cells (Src/Yes/Fyn deficient) and a Pyk2 mutant lacking the Src binding site, indicating direct inhibition. Activation of Pyk2 by biological stimuli correlates with dissociation of the endogenous FIP200-Pyk2 complex. FIP200 also inhibits Pyk2-induced apoptosis in intact cells. Yeast two-hybrid screen, in vitro binding assay, Co-immunoprecipitation, in vitro kinase assay The Journal of cell biology High 10769033
2000 Pyk2 inhibits G1-to-S phase transition (whereas FAK promotes it). This differential cell cycle regulation maps to the C-terminal domain of Pyk2 (chimeric PFhy1 with Pyk2 N-term/FAK C-term promotes cell cycle; FPhy2 with FAK N-term/Pyk2 C-term inhibits it). Pyk2 and FPhy2 stimulate JNK activation while inhibiting ERK activation in adhesion, linking these pathway differences to cell cycle outcomes. Pyk2 localizes to cytoplasm (not focal contacts), unlike FAK. Tetracycline-regulated expression, chimeric constructs, flow cytometry, kinase assays, immunofluorescence Journal of cell science Medium 10934044
2000 CADTK/Pyk2 localizes to the leading edge and ruffling lamellipodia of adherent human monocytes. Introduction of the dominant-negative C-terminal fragment CRNK inhibits CADTK autophosphorylation, reduces cell spreading, inhibits adhesion-induced phosphotyrosine increases and ERK activation, and reduces monocyte motility (from 83% to 26% motile cells). CRNK introduction does not affect phagocytosis or adhesion-induced cytokine gene induction. Immunocytochemistry, electroporation of dominant-negative construct (GST-CRNK), motility assay, ERK assay The Journal of biological chemistry High 11062241
2001 Nephrocystin forms protein complexes with Pyk2, p130(Cas), and tensin as shown by immunoprecipitation of native nephrocystin. Expression of nephrocystin results in phosphorylation of Pyk2 at tyrosine 402 and activation of downstream ERK1 and ERK2, suggesting nephrocystin recruits Pyk2 to cell-matrix adhesions. Immunoprecipitation, Western blot with phospho-specific antibody, ERK activation assay Proceedings of the National Academy of Sciences of the United States of America Medium 11493697
2001 Pyk2 tyrosine kinase activity is required for pulmonary vascular endothelial cell spreading, migration, morphogenesis, and pulmonary vein/artery angiogenesis ex vivo. Pyk2 kinase activity is required for expression of focal adhesion kinase, p130Crk-associated substrate, and HEF1, linking Pyk2 to focal adhesion formation and cytoskeletal reorganization. Adenovirus-mediated expression of Pyk2 mutants (kinase-dead), endothelial migration/morphogenesis assays, ex vivo angiogenesis assay, Western blot The Journal of biological chemistry Medium 11739395
2001 RAFTK/Pyk2 is co-immunoprecipitated with PI3K upon platelet activation, and thrombin, ADP, and collagen induce phosphorylation of both PI3K and RAFTK. At low thrombin doses, RAFTK phosphorylation and platelet aggregation are PI3K activity-dependent. SHP-2 (protein tyrosine phosphatase-2) associates with RAFTK upon platelet activation in a PI3K-dependent manner. Immunoprecipitation, kinase assay, pharmacological inhibitors (wortmannin), Western blot British journal of haematology Medium 11472358
2002 HRG stimulation of T47D breast cancer cells induces RAFTK association with p190 RhoGAP, RasGAP, and ErbB-2. RAFTK mediates Src-dependent tyrosine phosphorylation of p190, and mutation of the Src binding site (Y402) of RAFTK abolishes p190 phosphorylation. ErbB-2 association with RAFTK is indirect and mediated by Src. Wild-type RAFTK expression increases breast cancer cell invasion; kinase mutant RAFTK-R457 and Y402 mutant do not. Immunoprecipitation, site-directed mutagenesis, invasion assay, Western blot Oncogene Medium 10713673
2002 Pyk2 interacts with ARA55 (androgen receptor coregulator) and phosphorylates ARA55 at tyrosine 43, impairing ARA55 coactivator activity and/or sequestering ARA55 to reduce AR transactivation. This indirect modulation of androgen receptor function by Pyk2 was demonstrated by yeast two-hybrid, co-IP, and in vitro phosphorylation. Yeast two-hybrid, Co-immunoprecipitation, in vitro phosphorylation, transactivation assay The Journal of biological chemistry Medium 11856738
2002 Pyk2/RAFTK-mediated alpha-synuclein tyrosine phosphorylation at Y125 occurs in response to hyperosmotic stress, with Src-family kinases acting downstream of Pyk2 as the proximal kinases for alpha-synuclein. Dominant-negative Pyk2 reduces osmotic stress-induced alpha-synuclein phosphorylation. Western blot, dominant-negative Pyk2 construct, phospho-specific detection, site-directed mutagenesis of alpha-synuclein FEBS letters Medium 12096713
2002 In neonatal rat cardiomyocytes, adenoviral RAFTK/Pyk2 expression induces apoptosis via concurrent phosphorylation of Src, JNK, and p38, leading to PARP cleavage, caspase-3 activation, and DNA laddering. Mutation of the Y402 Src-binding site reduces DNA laddering. Wild-type or phosphorylation-deficient paxillin (mutated at Y31/Y118) prevents RAFTK-mediated apoptosis and preserves myofibril organization. Adenoviral expression, site-directed mutagenesis (Y402), caspase assay, PARP cleavage, paxillin rescue The Journal of biological chemistry Medium 15322113
2003 Pyk2 acts as a scaffold for Src-dependent phosphorylation of PDK1 on Tyr9, enabling subsequent Src phosphorylation of PDK1 on Tyr373 and Tyr376 downstream of angiotensin II in vascular smooth muscle cells. Pyk2 and tyrosine-phosphorylated PDK1 co-localize in focal adhesions after Ang II stimulation. A Tyr9 mutant of PDK1 inhibits Ang II-induced paxillin phosphorylation and focal adhesion formation. Adenoviral expression, site-directed mutagenesis of PDK1 (Y9), confocal co-localization, immunoprecipitation, Western blot Molecular and cellular biology Medium 14585963
2004 RAFTK/Pyk2 autophosphorylation occurs via a trans-acting (intermolecular) mechanism, not a cis-acting mechanism. Kinase-mutated RAFTK inhibits wild-type RAFTK autophosphorylation in a dose-dependent trans manner. Trans-autophosphorylation occurs only at Tyr402, and this is Src kinase activity-independent. Src significantly enhances RAFTK-mediated paxillin phosphorylation downstream of Tyr402. RAFTK self-associates, and this association is not dependent on a single domain. Dual-tag RAFTK constructs, immunoprecipitation, affinity chromatography, in vitro kinase assay, site-directed mutagenesis The Journal of biological chemistry High 15166227
2004 VEGF-induced p38 MAPK activation in endothelial cells is dependent on RAFTK/Pyk2 (dominant-negative Pyk2 reduces p38 activation) and is calcium-dependent (EGTA blocks it). Src family kinase activity is also required upstream of p38, and both Src and RAFTK/Pyk2 are essential for VEGF-induced endothelial cell migration. This pathway is distinct from PLC-dependent ERK activation. Dominant-negative Pyk2 expression, pharmacological inhibitors, kinase assay, migration assay Oncogene Medium 14676843
2005 Pyk2 autophosphorylation is necessary but not sufficient for glioma cell migration. The N-terminal domain of Pyk2 is required to stimulate migration (N-terminal deletion abolishes migration stimulation; autonomous N-terminal domain inhibits migration). Substitution of the Pyk2 C-terminal domain with the FAK C-terminal domain retains Pyk2-mediated migration stimulation, while substitution of the N-terminal domain with FAK N-terminus inhibits migration. siRNA silencing of Pyk2 inhibits glioma migration; re-expression of Pyk2 (but not FAK) restores it. Domain-swap chimeric constructs, siRNA knockdown, cell migration assay, RNA interference rescue Neoplasia Medium 15967096
2005 Loss of VE-cadherin function triggers Rac1 activation and ROS production, which activate Pyk2. Active Pyk2 is recruited to cell-cell junctions and phosphorylates VE-cadherin-associated beta-catenin on tyrosine. Expression of dominant-negative CRNK (N-terminal deletion mutant) abolishes the increase in beta-catenin tyrosine phosphorylation and prevents loss of endothelial cell-cell contact. Dominant-negative CRNK expression, phospho-specific Western blot, immunofluorescence, electrical resistance measurement The Journal of biological chemistry Medium 15778498
2005 SAPAP3 (SAP90/PSD-95-Associated Protein-3) interacts with FAK (residues 676-840) and PYK2 in yeast two-hybrid and GST pull-down assays. The three proteins co-distribute with PSD-95 and Src in postsynaptic density sucrose gradient fractions, suggesting SAPAP3 anchors PYK2 in postsynaptic densities. Yeast two-hybrid, GST pull-down, sucrose gradient fractionation Biochemical and biophysical research communications Medium 16202977
2008 PCDH-gamma (gamma-protocadherins) binds PYK2 and FAK, and this interaction inhibits kinase activity. PYK2 activity is abnormally upregulated in Pcdh-gamma-deficient neurons. Overexpression of PYK2 induces apoptosis in chicken spinal cord. PCDH-alpha also interacts with PYK2 and FAK despite a distinct cytoplasmic domain; in neural tissue, PCDH-gamma and PCDH-alpha form complexes with PYK2 and/or FAK. Co-immunoprecipitation, kinase assay in Pcdh-gamma-null neurons, overexpression in chick spinal cord The Journal of biological chemistry Medium 19047047
2009 Pyk2 phosphorylates and activates PDZ-RhoGEF in vitro. Knockdown of PDZ-RhoGEF reduces RhoA activation by constitutively active Pyk2, placing PDZ-RhoGEF downstream of Pyk2. Knockdown of PYK2 or PDZ-RhoGEF markedly decreases RhoA activation by calcium ionophore A23187, establishing a PYK2/PDZ-RhoGEF/RhoA axis linking Ca2+ signaling to RhoA activation in vascular smooth muscle cells. In vitro phosphorylation/activation assay, adenoviral knockdown, RhoA translocation assay, Western blot Arteriosclerosis, thrombosis, and vascular biology Medium 19759375
2009 PYK2 interacts with MyD88 via MyD88's death domain (in vitro and in macrophages). PYK2-deficient macrophages exhibit reduced IκB phosphorylation/degradation, decreased NF-κB activation, and decreased IL-1β expression in response to LPS, placing PYK2 in the LPS-MyD88-NF-κB signaling pathway. Co-immunoprecipitation, domain mapping (death domain), Western blot in PYK2-deficient macrophages Journal of leukocyte biology Medium 19955209
2010 PSD-95 overexpression in PC6-3 cells induces trans-autophosphorylation of Pyk2 at Tyr402. In neurons, Ca2+ influx through NMDA receptors causes postsynaptic clustering and autophosphorylation of endogenous Pyk2 via Ca2+- and calmodulin-stimulated binding to PSD-95. This Pyk2 activation mechanism is critical for long-term potentiation in hippocampal CA1. Overexpression, in vitro oligomerization (antibody-induced), calcium imaging, LTP electrophysiology, immunofluorescence in neurons The Journal of neuroscience High 20071509
2010 Pyk2 interacts with mGluR1 and mGluR5, precipitated from rat brain. Pyk2 associates with the second intracellular loop and distal C-terminal tail of mGluR1a (GST pull-down). Pyk2 overexpression attenuates agonist-stimulated inositol phosphate formation by displacing Galphaq/11 from the receptor. Pyk2 activity (calmodulin-, Src-, and PKC-dependent) is required for mGluR-stimulated ERK1/2 phosphorylation. Co-immunoprecipitation from rat brain, GST pull-down, IP formation assay, dominant-negative Pyk2, ERK assay Molecular brain Medium 20180987
2012 STEP (striatal-enriched protein-tyrosine phosphatase) binds to Pyk2 and dephosphorylates it at Tyr402. STEP KO mice show enhanced phosphorylation of Pyk2 at Tyr402 and of its substrates paxillin and ASAP1. STEP opposes Pyk2 activation after KCl depolarization and blocks Pyk2 translocation to postsynaptic densities. Co-immunoprecipitation, phosphatase assay, Western blot in STEP KO mice, biochemical fractionation The Journal of biological chemistry High 22544749
2015 FAK and PYK2 phosphorylate GSK3β at Y216, promoting β-catenin accumulation and Wnt/β-catenin pathway activation, and intestinal tumorigenesis in APCmin/+ mice. Phosphorylation of GSK3β(Y216) acts as a molecular determinant for GSK3β recruitment of β-TrCP. Pharmacological FAK/PYK2 inhibition suppresses adenoma formation in APCmin/+ mice with reduced phospho-GSK3β(Y216) and β-catenin. In vitro kinase assay, mutagenesis, APCmin/+ mouse model, pharmacological inhibition eLife High 26274564
2015 EGF induces rapid phosphorylation of PYK2 and its translocation to early endosomes where it co-localizes with EGFR and sustains downstream signals. PYK2 enhances EGF-induced STAT3 phosphorylation, while phospho-STAT3 directly binds to the PYK2 promoter to regulate PYK2 transcription. PYK2 and STAT3 also enhance c-Met expression, while c-Met augments their phosphorylation, forming a positive feedback loop. Immunofluorescence/confocal microscopy for co-localization with endosomes, ChIP for STAT3 binding to PYK2 promoter, Western blot, siRNA knockdown Nature communications Medium 25648557
2015 Pyk2 is required for astrocyte migration after brain lesion. Pyk2-/- astrocytes migrated slower in in vitro wound healing and had delayed actin re-polymerization after latrunculin B treatment. Gelsolin was less enriched at the leading edge of migrating Pyk2-/- astrocytes, suggesting its lack of recruitment partially mediates the migration defect. TNFα-induced Pyk2 phosphorylation at Tyr402 increased PKC activity upstream. Pyk2 knockout mice, in vivo stab lesion, in vitro wound healing, actin dynamics assay, immunofluorescence Glia Medium 26663135
2017 Pyk2 co-localizes with cortactin at invadopodia and mediates EGF-induced cortactin tyrosine phosphorylation directly and indirectly via Src-mediated Arg kinase activation. This leads to actin polymerization in invadopodia, ECM degradation, and tumor cell invasion. siRNA knockdown and rescue experiments established Pyk2 as regulator of invadopodium-mediated functions, distinct from FAK which regulates focal adhesion-mediated motility. Protein array screening, Co-immunoprecipitation, siRNA knockdown, in vitro kinase assay, confocal microscopy, invasion assay The Journal of cell biology High 29133485
2018 Pyk2 is a direct tyrosine kinase of tau protein, phosphorylating tau in vitro and in vivo. Pyk2 colocalizes, interacts with, and phosphorylates tau. Pyk2 activity is increased in FynCA (constitutively active Fyn) mice and decreased in FynKO mice, placing Pyk2 downstream of Fyn in a tau phosphorylation cascade. In vitro kinase assay, Co-immunoprecipitation, transgenic mouse models (Pyk2/tau double transgenic, FynCA, FynKO), Western blot with phospho-tau antibodies Journal of Alzheimer's disease Medium 29782321
2018 Alpha-protocadherins (Pcdha) regulate cortical neuron migration through the WAVE complex, and Pyk2 overexpression impairs cortical neuron migration via inactivation of the small GTPase Rac1, defining a molecular Pcdhα/WAVE/Pyk2/Rac1 axis in actin cytoskeletal dynamics. Pcdha cluster knockout mice, Pyk2 overexpression, Rac1 activity assay, cortical neuron migration assay eLife Medium 29911975
2018 PYK2 positively regulates TAZ (and YAP) transcriptional activity in triple-negative breast cancer. PYK2 inhibition or knockdown facilitates proteasomal degradation of TAZ; this is specific to PYK2 and not observed with FAK inhibition. PYK2 enhances tyrosine phosphorylation of both TAZ and LATS1/2, promoting TAZ stability. siRNA knockdown, kinase inhibitor, Western blot, proteasomal degradation assay, transcriptional reporter Cell death & disease Medium 30250159
2019 Pyk2 interacts with the RhoGAP protein Graf1c in brain tissue (biochemical isolation), and Pyk2 kinase activity inhibits Graf1c, thereby activating RhoA. Aβ oligomer-induced reductions in dendritic spine motility and chronic spine loss require both Pyk2 kinase activity and RhoA activation, establishing a Pyk2/Graf1/RhoA pathway in synapse maintenance. Biochemical isolation of Pyk2-interacting proteins from brain, Co-immunoprecipitation, kinase assay, dendritic spine imaging, RhoA activity assay The Journal of neuroscience Medium 30626696
2020 CD56 (NCAM) on NK cells is functionally linked to Pyk2: CD56-knockout NK92 cells show decreased Pyk2 Tyr402 phosphorylation, impaired lytic granule exocytosis, and impaired immunological synapse polarization. Cytotoxicity, exocytosis, and Pyk2 Tyr402 phosphorylation are all rescued by CD56 re-introduction. CRISPR/Cas9 knockout of CD56, rescue re-expression, Western blot (phospho-Y402), cytotoxicity assay, granule exocytosis assay, immunological synapse imaging eLife High 32510326
2020 Pyk2 phosphorylates Cx43 (connexin 43) at residues Y247, Y265, Y267, and Y313 (identified by mass spectrometry). Pyk2 can be activated by Src and active Pyk2 interacts with Cx43 at the plasma membrane. Overexpression of Pyk2 increases Cx43 phosphorylation; knockdown decreases it. PMA-induced Pyk2 activation decreases Cx43 gap junction intercellular communication (GJIC), and Pyk2 inhibition partially restores GJIC. In vitro phosphorylation screen, mass spectrometry, Western blot, immunofluorescence, dye transfer GJIC assay in HeLaCx43 cells and NRVMs Journal of molecular and cellular cardiology Medium 32956670
2021 PKM2 promotes Pyk2 activation in macrophages downstream of TLR4, TLR7, and TLR9 pathways. Overexpression of PKM2 promotes TLR-induced Pyk2 activation, while PKM2 inhibition reduces it; co-immunoprecipitation showed PKM2-Pyk2 interaction. Pyk2 inhibitor phenocopied PKM2 inhibition in TLR pathway suppression. Co-immunoprecipitation, overexpression, siRNA, pharmacological inhibitor (Pyk2 inhibitor), Western blot, cytokine assay Frontiers in immunology Low 34025679
2021 PYK2 directly phosphorylates IRF5 (demonstrated by kinase inhibitor library screening and PYK2-deficient macrophage experiments). PYK2-deficient macrophages display impaired IRF5 activation and reduced inflammatory gene expression. The PYK2 inhibitor defactinib induces a transcriptomic signature similar to IRF5 deficiency and reduces pro-inflammatory cytokines in human colon biopsies and mouse colitis. Kinase inhibitor library screen, PYK2-deficient macrophages, transcriptomics, ex vivo human colon biopsy, mouse colitis model Nature communications Medium 34795257
2022 PYK2 senses calcium through its kinase-FAT linker (KFL), which is disordered and contains an unusual calmodulin (CaM) binding element. KFL engages CaM through an ensemble of transient interactions, and calcium increases the association by promoting structural changes in CaM exposing auxiliary interaction sites. KFL forms fuzzy dimers that are enhanced by CaM binding. As a monomer, KFL associates with the PYK2 FERM-kinase fragment. CaM-induced dimerization promotes trans-autophosphorylation-based PYK2 activation. NMR spectroscopy, biophysical binding assays, structural analysis, mutagenesis Communications biology High 35945264
2022 SIRPα forms a direct interaction with PTK2B/PYK2 through SIRPα's intracellular C-terminal domain, inhibiting PTK2B activation in macrophages. Necroptosis inhibition from SIRPα deficiency requires PTK2B activity, establishing PTK2B as a downstream effector of SIRPα signaling in macrophage homeostasis. Co-immunoprecipitation, domain mapping, PTK2B activity assay, SIRPα-/- macrophages, necroptosis assay EBioMedicine Medium 36202053
2022 Pyk2 deletion in PS19 tauopathy mice exacerbates tau phosphorylation, tau accumulation, synapse loss, gliosis, and spatial memory impairment. Endogenous Pyk2 suppresses LKB1 and p38 MAPK activity, providing a mechanism by which Pyk2 loss leads to increased tau pathology. Thus, in tauopathy, endogenous Pyk2 suppresses rather than promotes tau phosphorylation. Pyk2 conditional knockout in PS19 mice, proteomic profiling, phospho-tau Western blot, LKB1/p38 activity assays, behavioral testing Molecular neurodegeneration Medium 35501917
2023 PTK2B directly phosphorylates TBK1 at Tyr591, increasing TBK1 oligomerization and activation. PTK2B also interacts with STING and promotes its oligomerization in a kinase-independent manner. PTK2B depletion reduces antiviral signaling in fibroblasts, macrophages, and dendritic cells, and Ptk2b-deficient mice are more susceptible to viral infection. In vitro kinase assay, Co-immunoprecipitation, Ptk2b-/- mice, viral infection assay, oligomerization assay Nature communications High 37989995
2023 Mettl3/Ythdf2 regulate macrophage inflammation and ROS generation through Pyk2 mRNA stability. Mettl3 and Ythdf2 depletion increased Pyk2 mRNA stability and expression; RIP-PCR showed Ythdf2 directly targets Pyk2 mRNA in a Mettl3-dependent manner. Upregulated inflammatory signaling in Mettl3-knockdown cells was rescued by Pyk2 inhibitor, placing Pyk2 downstream of the Mettl3/Ythdf2 m6A axis. RNA-seq, RIP-PCR, siRNA knockdown, mRNA stability assay, pharmacological Pyk2 inhibition Immunology letters Medium 37952687

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 RAFTK/Pyk2-mediated cellular signalling. Cellular signalling 399 10704819
1995 Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain. The Journal of biological chemistry 322 7499242
1996 Activation of Pyk2 by stress signals and coupling with JNK signaling pathway. Science (New York, N.Y.) 282 8670418
2004 Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. Proceedings of the National Academy of Sciences of the United States of America 214 14976243
2000 Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins. Nature cell biology 184 10980697
1999 FAK and PYK2/CAKbeta in the nervous system: a link between neuronal activity, plasticity and survival? Trends in neurosciences 165 10354603
1996 Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes. Blood 154 8695788
2005 The tyrosine kinase pyk2 promotes migration and invasion of glioma cells. Neoplasia (New York, N.Y.) 115 15967096
2015 FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β. eLife 108 26274564
1998 Beta-chemokine receptor CCR5 signals via the novel tyrosine kinase RAFTK. Blood 107 9446638
2004 RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner. The Journal of biological chemistry 105 15166227
2005 Proline-rich tyrosine kinase 2 (Pyk2) mediates vascular endothelial-cadherin-based cell-cell adhesion by regulating beta-catenin tyrosine phosphorylation. The Journal of biological chemistry 97 15778498
1999 RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells. Oncogene 96 10597281
1998 Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America 92 9560226
2001 Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2. Proceedings of the National Academy of Sciences of the United States of America 90 11493697
2010 Targeting Pyk2 for therapeutic intervention. Expert opinion on therapeutic targets 89 20001213
2000 RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion. Oncogene 87 10713673
1997 RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes. The Journal of experimental medicine 87 9091579
2010 Anti-angiogenic genistein inhibits VEGF-induced endothelial cell activation by decreasing PTK activity and MAPK activation. Medical oncology (Northwood, London, England) 79 21132400
2008 alpha- and gamma-Protocadherins negatively regulate PYK2. The Journal of biological chemistry 72 19047047
2003 Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions. Molecular and cellular biology 71 14585963
2012 Striatal-enriched protein-tyrosine phosphatase (STEP) regulates Pyk2 kinase activity. The Journal of biological chemistry 70 22544749
2000 Pyk2 and FAK differentially regulate progression of the cell cycle. Journal of cell science 70 10934044
1998 Role of calcium-sensitive tyrosine kinase Pyk2/CAKbeta/RAFTK in angiotensin II induced Ras/ERK signaling. Hypertension (Dallas, Tex. : 1979) 70 9774361
1997 Tyrosine phosphorylation of the novel protein-tyrosine kinase RAFTK during an early phase of platelet activation by an integrin glycoprotein IIb-IIIa-independent mechanism. The Journal of biological chemistry 70 9099753
2002 Role of EGF Receptor and Pyk2 in endothelin-1-induced ERK activation in rat cardiomyocytes. Journal of molecular and cellular cardiology 68 11851354
2001 Protein-tyrosine kinase Pyk2 mediates endothelin-induced p38 MAPK activation in glomerular mesangial cells. The Journal of biological chemistry 66 11278444
2000 Suppression of Pyk2 kinase and cellular activities by FIP200. The Journal of cell biology 66 10769033
2015 PYK2 sustains endosomal-derived receptor signalling and enhances epithelial-to-mesenchymal transition. Nature communications 65 25648557
2010 Postsynaptic clustering and activation of Pyk2 by PSD-95. The Journal of neuroscience : the official journal of the Society for Neuroscience 65 20071509
2005 Negative regulation of PTK signalling by Cbl proteins. Growth factors (Chur, Switzerland) 60 16019438
2004 Vascular endothelial growth factor-mediated activation of p38 is dependent upon Src and RAFTK/Pyk2. Oncogene 60 14676843
1997 Cytokine signaling through the novel tyrosine kinase RAFTK in Kaposi's sarcoma cells. The Journal of clinical investigation 60 9120025
2018 Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development. Cancers 58 29891810
2004 Regulation of endothelial cell function BY FAK and PYK2. Frontiers in bioscience : a journal and virtual library 58 14977542
2014 Pyk2 promotes tumor progression in multiple myeloma. Blood 56 25217697
2009 PYK2/PDZ-RhoGEF links Ca2+ signaling to RhoA. Arteriosclerosis, thrombosis, and vascular biology 56 19759375
2017 Pyk2 and FAK differentially regulate invadopodia formation and function in breast cancer cells. The Journal of cell biology 55 29133485
1998 Paxillin phosphorylation and association with Lck and Pyk2 in anti-CD3- or anti-CD45-stimulated T cells. The Journal of biological chemistry 55 9488700
2000 Characterization of the tyrosine kinases RAFTK/Pyk2 and FAK in nerve growth factor-induced neuronal differentiation. The Journal of biological chemistry 52 10764815
2020 CD56 regulates human NK cell cytotoxicity through Pyk2. eLife 51 32510326
2004 Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kinase is antagonized by paxillin. The Journal of biological chemistry 50 15322113
2021 The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases. Frontiers in synaptic neuroscience 48 34690733
2018 PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease. Experimental neurology 48 29803828
1997 Activation of protein-tyrosine kinase Pyk2 is downstream of Syk in FcepsilonRI signaling. The Journal of biological chemistry 47 9405454
2018 Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice. eLife 46 29911975
2002 Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator. The Journal of biological chemistry 46 11856738
2000 Inhibition of the calcium-dependent tyrosine kinase (CADTK) blocks monocyte spreading and motility. The Journal of biological chemistry 46 11062241
1998 The related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated and participates in colony-stimulating factor-1/macrophage colony-stimulating factor signaling in monocyte-macrophages. Blood 45 9573036
2019 Pyk2 Signaling through Graf1 and RhoA GTPase Is Required for Amyloid-β Oligomer-Triggered Synapse Loss. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 30626696
2014 Pyk2 and Src mediate signaling to CCL18-induced breast cancer metastasis. Journal of cellular biochemistry 43 24142406
2018 Role of Pyk2 in Human Cancers. Medical science monitor : international medical journal of experimental and clinical research 42 30425234
2002 Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion kinase in cardiac remodeling. The Journal of biological chemistry 42 12228222
2021 Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation. Frontiers in immunology 41 34025679
2001 Pyk2/CAKbeta tyrosine kinase activity-mediated angiogenesis of pulmonary vascular endothelial cells. The Journal of biological chemistry 40 11739395
2015 Targeting PYK2 mediates microenvironment-specific cell death in multiple myeloma. Oncogene 38 26387544
2008 The tyrosine kinase Pyk2 mediates lipopolysaccharide-induced IL-8 expression in human endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 38 18390748
2018 Pyk2 is a Novel Tau Tyrosine Kinase that is Regulated by the Tyrosine Kinase Fyn. Journal of Alzheimer's disease : JAD 37 29782321
2007 The acid-activated signaling pathway: starting with Pyk2 and ending with increased NHE3 activity. Kidney international 37 17882150
2001 Pyk2 expression and phosphorylation in neonatal and adult cardiomyocytes. Journal of molecular and cellular cardiology 37 11343423
2010 Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation. Molecular brain 36 20180987
2014 Adaptors for disorders of the brain? The cancer signaling proteins NEDD9, CASS4, and PTK2B in Alzheimer's disease. Oncoscience 35 25594051
2024 Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aβ pathology through microglial and astroglial cells. Brain pathology (Zurich, Switzerland) 34 38247340
2010 Stretch augments TGF-beta1 expression through RhoA/ROCK1/2, PTK, and PI3K in airway smooth muscle cells. American journal of physiology. Lung cellular and molecular physiology 34 20511342
2002 Activation of Pyk2/RAFTK induces tyrosine phosphorylation of alpha-synuclein via Src-family kinases. FEBS letters 34 12096713
2022 Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway. Journal of orthopaedic translation 33 35228997
2009 PYK2 interacts with MyD88 and regulates MyD88-mediated NF-kappaB activation in macrophages. Journal of leukocyte biology 33 19955209
1999 From PTK-STAT signaling to caspase expression and apoptosis induction. Cell death and differentiation 33 10637436
2022 Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy. Molecular neurodegeneration 32 35501917
2018 PYK2 negatively regulates the Hippo pathway in TNBC by stabilizing TAZ protein. Cell death & disease 32 30250159
2009 Src family protein tyrosine kinase (PTK) modulates the effect of SGK1 and WNK4 on ROMK channels. Proceedings of the National Academy of Sciences of the United States of America 31 19706464
2003 Differential role of PTK and ERK MAPK in superoxide impairment of K(ATP) and K(Ca) channel cerebrovasodilation. American journal of physiology. Regulatory, integrative and comparative physiology 31 12793995
2009 Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways. Journal of cellular biochemistry 30 19415692
2021 Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation. Nature communications 27 34795257
2015 Pyk2 is essential for astrocytes mobility following brain lesion. Glia 26 26663135
2019 Pyk2 in the amygdala modulates chronic stress sequelae via PSD-95-related micro-structural changes. Translational psychiatry 25 30664624
2015 Pyk2 and Megakaryocytes Regulate Osteoblast Differentiation and Migration Via Distinct and Overlapping Mechanisms. Journal of cellular biochemistry 25 26552846
1997 Characterization of the novel focal adhesion kinase RAFTK in hematopoietic cells. Leukemia & lymphoma 25 9402324
2022 SIRPα maintains macrophage homeostasis by interacting with PTK2B kinase in Mycobacterium tuberculosis infection and through autophagy and necroptosis. EBioMedicine 23 36202053
2019 PYK2 promotes HER2-positive breast cancer invasion. Journal of experimental & clinical cancer research : CR 23 31118051
2003 PYK2 and FAK in osteoclasts. Frontiers in bioscience : a journal and virtual library 23 12957821
2023 PYK2, a hub of signaling networks in breast cancer progression. Trends in cell biology 22 37586982
2007 Src and Pyk2 mediate angiotensin II effects in cultured rat astrocytes. Regulatory peptides 22 17391778
2001 RAFTK/Pyk2 involvement in platelet activation is mediated by phosphoinositide 3-kinase. British journal of haematology 22 11472358
1997 v-Abl protein tyrosine kinase (PTK) mediated suppression of apoptosis is associated with the up-regulation of Bcl-XL. Oncogene 22 9393984
2022 Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice. Frontiers in immunology 21 35178052
2021 Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation. Cancers 21 34944779
2019 Three Novel Players: PTK2B, SYK, and TNFRSF21 Were Identified to Be Involved in the Regulation of Bovine Mastitis Susceptibility via GWAS and Post-transcriptional Analysis. Frontiers in immunology 21 31447828
2016 The Tyrosine Kinase Pyk2 Contributes to Complement-Mediated Phagocytosis in Murine Macrophages. Journal of innate immunity 21 26848986
2012 Megakaryocytes regulate expression of Pyk2 isoforms and caspase-mediated cleavage of actin in osteoblasts. The Journal of biological chemistry 21 22447931
2008 Expression of tetraspan protein CD63 activates protein-tyrosine kinase (PTK) and enhances the PTK-induced inhibition of ROMK channels. The Journal of biological chemistry 21 18211905
2005 FAK and PYK2 interact with SAP90/PSD-95-Associated Protein-3. Biochemical and biophysical research communications 21 16202977
2023 Mettl3/Ythdf2 regulate macrophage inflammation and ROS generation by controlling Pyk2 mRNA stability. Immunology letters 20 37952687
2023 PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling. Nature communications 20 37989995
2020 Inhibition of Pyk2 and Src activity improves Cx43 gap junction intercellular communication. Journal of molecular and cellular cardiology 19 32956670
2002 The role of Aktand RAFTK in beta1 integrin mediated survival of precursor B-acute lymphoblastic leukemia cells. Leukemia & lymphoma 19 12400610
2022 PYK2 senses calcium through a disordered dimerization and calmodulin-binding element. Communications biology 18 35945264
2022 Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis. International journal of molecular sciences 18 36555115
2016 Common variant in PTK2B is associated with late-onset Alzheimer's disease: A replication study and meta-analyses. Neuroscience letters 18 27080426
2002 Csk homologous kinase associates with RAFTK/Pyk2 in breast cancer cells and negatively regulates its activation and breast cancer cell migration. International journal of oncology 18 12063569

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