Affinage

PTK2B

Protein-tyrosine kinase 2-beta · UniProt Q14289

Length
1009 aa
Mass
115.9 kDa
Annotated
2026-04-28
100 papers in source corpus 53 papers cited in narrative 53 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTK2B/Pyk2 is a calcium-sensitive non-receptor tyrosine kinase that transduces signals from integrins, G-protein-coupled receptors, growth factor receptors, and immune receptors into cytoskeletal reorganization, cell migration, inflammatory gene expression, and synaptic plasticity. Activation proceeds through Src-mediated priming phosphorylation at Tyr402 followed by FERM domain–regulated oligomerization and trans-autophosphorylation, creating docking sites for Src-family kinases, p130Cas, paxillin, PI3K, and Graf1c to relay signals to JNK, p38 MAPK, ERK, NF-κB, RhoA, and Wnt/β-catenin pathways (PMID:8670418, PMID:26866924, PMID:20849950, PMID:20071509, PMID:11435419, PMID:26274564). In immune cells, Pyk2 is essential for macrophage polarization and chemotactic migration, CR3-mediated phagocytosis, NLRP3 inflammasome activation via direct ASC Tyr146 phosphorylation, IRF5-dependent inflammatory transcription, and STING–TBK1 antiviral signaling (PMID:12960403, PMID:26848986, PMID:27796369, PMID:34795257, PMID:37989995). In the nervous system, PSD-95–mediated Pyk2 clustering at postsynaptic densities drives NMDA receptor–dependent LTP, while Pyk2-dependent inhibition of Graf1c/RhoA controls dendritic spine density, and Pyk2 directly phosphorylates tau; loss of Pyk2 in tauopathy models exacerbates tau pathology and cognitive decline (PMID:20071509, PMID:30626696, PMID:29782321, PMID:35501917).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Establishing that Pyk2 is a stress-responsive kinase upstream of JNK resolved how diverse extracellular stresses converge on MAPK cascades through a non-receptor tyrosine kinase.

    Evidence Dominant-negative Pyk2 blocked UV- and osmotic-shock-induced JNK activation in transfected cells

    PMID:8670418

    Open questions at the time
    • Mechanism linking stress stimuli to Pyk2 activation was unresolved
    • Direct kinase substrates not identified
  2. 1997 High

    Identification of Pyk2 activation by TCR, integrins, and thrombin—with calcium and PKC dependence—established Pyk2 as a convergence node for receptor-proximal signaling across immune and hemostatic cells.

    Evidence TCR-stimulated co-IP with Fyn/Grb2/paxillin in T cells; thrombin-induced Ca²⁺/PKC-dependent Pyk2 phosphorylation in platelets; Syk-dependent and -independent activation in mast cells

    PMID:9091579 PMID:9099753 PMID:9405454

    Open questions at the time
    • Direct substrates downstream of Pyk2 in these cells were unknown
    • Whether Pyk2 activation mechanism involved autophosphorylation or trans-phosphorylation was unresolved
  3. 1998 High

    Demonstrating that Src physically binds and phosphorylates Pyk2 (>20-fold enhancement), and that chemokine receptor signaling through Pyk2 activates JNK/p38 via paxillin, defined the Src–Pyk2 partnership and downstream MAPK relay.

    Evidence In vitro kinase assays and SH2 domain binding in osteoblastic cells; dominant-negative Pyk2 blocking CCR5-induced JNK/p38 in hematopoietic cells

    PMID:9446638 PMID:9556630 PMID:9774361

    Open questions at the time
    • Whether Src phosphorylation is a priming or amplification step was unclear
    • Mechanism of Ca²⁺/calmodulin-dependent Pyk2 activation remained undefined
  4. 1999 High

    Discovery of p130Cas–Pyk2 complex at osteoclast podosomes and of Pyk2-mediated apoptosis in myeloma cells broadened Pyk2's functional scope to cytoskeletal adhesion structures and cell death regulation.

    Evidence Co-IP and immunofluorescence at sealing zones/podosomes; kinase-dead Pyk2 rescued dexamethasone-induced apoptosis

    PMID:10597281 PMID:9988732

    Open questions at the time
    • Direct phosphorylation targets at adhesion sites not mapped
    • Pathway from Pyk2 kinase activity to apoptotic execution not delineated
  5. 2000 High

    Pyk2 was placed at the intersection of adhesion, growth factor, and immune receptor signaling through studies showing its podosomal localization in macrophages (required for migration), cooperation with EGF receptor/integrins in neurite outgrowth, NGF-induced translocation, and TCR-proximal JNK/p38 signaling for IL-2 production.

    Evidence Antisense knockdown blocking macrophage migration; domain chimeras in neurite assays; Pyk2-Y402F inhibiting TCR-induced IL-2/JNK/p38; FIP200 binding and inhibiting Pyk2 kinase activity and apoptosis

    PMID:10764815 PMID:10769033 PMID:10867021 PMID:10934044 PMID:10980697 PMID:11056520

    Open questions at the time
    • How Pyk2 drives cell polarization mechanistically was unknown
    • Structural basis of FERM domain autoinhibition not established
  6. 2001 High

    Linking Pyk2 to NF-κB via Gq/G13–PI3K/Akt and to TLR signaling via MyD88 interaction established Pyk2 as a central relay in inflammatory transcription factor activation.

    Evidence Kinase-dead Pyk2 blocking NF-κB reporter and Akt activation; PYK2-deficient macrophages showing impaired IκB degradation upon LPS; co-IP of Pyk2 with MyD88 death domain

    PMID:11278444 PMID:11435419 PMID:19955209

    Open questions at the time
    • Whether Pyk2 directly phosphorylates IKK complex components was untested
    • Mechanism of Pyk2 engagement by MyD88 at the structural level unknown
  7. 2002 High

    Identification of ARA55 as a direct Pyk2 substrate (Tyr43) that modulates androgen receptor transactivation extended Pyk2's reach into nuclear hormone receptor signaling.

    Evidence Yeast two-hybrid, in vitro phosphorylation at defined site, AR reporter assay

    PMID:11856738

    Open questions at the time
    • In vivo relevance of Pyk2–ARA55 axis for androgen signaling not tested
    • Whether Pyk2 nuclear entry is needed for this function was unresolved
  8. 2003 High

    Pyk2 knockout macrophages demonstrated that Pyk2 is non-redundant with FAK for cell polarization, chemotaxis, Rho activation, and PI3K signaling, establishing it as an essential node in innate immune cell motility.

    Evidence Homologous recombination KO with chemotaxis, Ca²⁺ imaging, Rho GTPase, and PI3K assays

    PMID:12960403

    Open questions at the time
    • Specific Rho GEF/GAP regulated by Pyk2 in macrophages not identified
    • Whether Pyk2 controls migration in vivo during infection was untested
  9. 2010 High

    Mechanistic reconstitution showed that PSD-95-driven Pyk2 oligomerization enables trans-autophosphorylation at Tyr402, providing the activation mechanism for NMDA receptor–dependent LTP; concurrently, the FERM domain was shown to regulate oligomer formation, and STEP was identified as the opposing phosphatase.

    Evidence In vitro oligomerization assay plus LTP electrophysiology; FERM domain competition experiments; in vitro STEP phosphatase assay with KO mouse validation

    PMID:20071509 PMID:20849950 PMID:22544749

    Open questions at the time
    • Crystal structure of the Pyk2 autoinhibited dimer was unavailable
    • Whether STEP–Pyk2 regulation occurs at all synapses or is region-specific was unknown
  10. 2013 High

    Pyk2 KO platelets revealed essential roles in integrin αIIbβ3 outside-in signaling (PI3Kβ/Akt, Rap1b activation), and MAP4K4 was identified as a Pyk2 FERM-binding partner and co-effector in glioma migration.

    Evidence Pyk2 KO platelet spreading assays with PI3K activity; yeast two-hybrid plus co-IP and epistatic migration assays for MAP4K4

    PMID:23216754 PMID:24163766

    Open questions at the time
    • Whether Pyk2 directly phosphorylates MAP4K4 at a defined site was not resolved
    • In vivo thrombosis phenotype of Pyk2 KO not fully characterized
  11. 2015 High

    Pyk2 (redundantly with FAK) directly phosphorylates GSK3β at Tyr216, reinforcing Wnt/β-catenin signaling and intestinal adenoma formation, while Pyk2 endosomal translocation upon EGF forms a STAT3 positive-feedback loop sustaining its own expression.

    Evidence In vitro kinase assay plus APCmin/+ mouse pharmacological inhibition; confocal imaging of endosomal Pyk2/EGFR, ChIP of pSTAT3 on PTK2B promoter

    PMID:25648557 PMID:26274564

    Open questions at the time
    • Whether Pyk2 or FAK is the dominant GSK3β kinase in specific tissues was unresolved
    • Endosomal Pyk2 substrates beyond STAT3 pathway not mapped
  12. 2016 High

    Ordered Pyk2 activation was clarified: Src primes Tyr402, which is prerequisite for Tyr579 phosphorylation and full trans-autophosphorylation; separately, Pyk2 was shown essential for CR3-mediated but not FcγR-mediated phagocytosis, and to directly phosphorylate ASC Tyr146 for NLRP3 inflammasome assembly.

    Evidence Src inhibitors/genetic mutants ordering phosphorylation events; CRISPR KO phagocytosis assays; in vitro kinase assay on ASC with site mutagenesis and speck imaging

    PMID:26848986 PMID:26866924 PMID:27796369

    Open questions at the time
    • Structural basis of Src–Pyk2 priming interaction not visualized
    • Whether Pyk2-ASC axis operates in non-canonical inflammasomes untested
  13. 2017 High

    Pyk2 was distinguished from FAK at the subcellular level: Pyk2 drives invadopodium-mediated ECM degradation and tumor invasion by phosphorylating cortactin and activating Arg/Src, whereas FAK controls focal adhesion–based motility.

    Evidence Protein array screen, in vitro kinase assay on cortactin, invadopodium degradation assays, siRNA knockdown

    PMID:29133485

    Open questions at the time
    • In vivo tumor metastasis dependence on Pyk2 versus FAK not dissected genetically
  14. 2018 High

    Pyk2 was shown to directly phosphorylate tau and to regulate TAZ/YAP stability in breast cancer, extending its substrate repertoire to neurodegeneration-relevant and Hippo pathway targets.

    Evidence In vitro tau phosphorylation plus Fyn-transgenic mouse models; siRNA/pharmacological inhibition with proteasome rescue for TAZ

    PMID:29782321 PMID:30250159

    Open questions at the time
    • Specific tau phosphorylation sites targeted by Pyk2 not fully mapped
    • Whether Pyk2 directly phosphorylates LATS1/2 or acts indirectly was unresolved
  15. 2019 High

    Identification of Graf1c as a Pyk2-interacting RhoGAP in brain revealed the mechanism by which Pyk2 controls RhoA activity and dendritic spine density, and how amyloid-β oligomers cause spine loss through Pyk2-dependent Graf1c inhibition.

    Evidence Brain biochemical isolation, co-IP, spine imaging, Pyk2 kinase inhibition and RhoA epistasis

    PMID:30626696

    Open questions at the time
    • Whether Pyk2 directly phosphorylates Graf1c was not shown
    • Relevance of this pathway in human Alzheimer's disease tissue not demonstrated
  16. 2021 High

    Pyk2 was established as a direct kinase for IRF5 (inflammatory transcription) and TBK1 Tyr591 (antiviral innate immunity via STING), unifying its roles in inflammation and host defense; Pyk2 also promotes STING oligomerization kinase-independently.

    Evidence KO macrophage transcriptomics and in vivo colitis model for IRF5; in vitro kinase assay on TBK1 with site mutagenesis and Ptk2b−/− mice infected with virus

    PMID:34795257 PMID:37989995

    Open questions at the time
    • Whether Pyk2 activates other IRF family members is untested
    • Structural basis of kinase-independent STING oligomerization by Pyk2 unknown
  17. 2022 High

    Conditional Pyk2 deletion in a tauopathy model unexpectedly worsened tau pathology by de-repressing LKB1 and p38 MAPK, revealing a protective role for endogenous Pyk2 against tau accumulation and cognitive decline.

    Evidence Pyk2 conditional KO in PS19 mice with phospho-tau analysis, proteomics, and behavioral testing

    PMID:35501917

    Open questions at the time
    • Mechanism by which Pyk2 suppresses LKB1 activity not elucidated
    • Whether this protective role is neuron-autonomous or involves glia is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length autoinhibited Pyk2 structure, how the FERM domain senses calcium to relieve autoinhibition, the complete in vivo substrate phosphoproteome, and the relative contributions of Pyk2 versus FAK in specific tissues during disease.
  • No full-length Pyk2 crystal or cryo-EM structure available
  • Comprehensive in vivo phosphoproteomics of Pyk2-dependent signaling lacking
  • Tissue-specific Pyk2 versus FAK redundancy not systematically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 1 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-168256 Immune System 7 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 4 R-HSA-109582 Hemostasis 3 R-HSA-112316 Neuronal System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
BCAR1FYNGRAF1MYD88PSD95PXNSRCSTING1
Complex memberships
podosome/invadopodium complexpostsynaptic density

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Pyk2 is activated by stress signals (TNF-alpha, UV irradiation, osmotic shock) and functions as an upstream mediator of the JNK signaling pathway; a dominant-negative Pyk2 mutant blocked UV- or osmotic shock-induced JNK activation. Dominant-negative overexpression, stress stimulation assays Science High 8670418
1997 RAFTK/Pyk2 is rapidly phosphorylated upon T cell receptor activation in T cells, leading to increased association with Fyn and Grb2 (via their SH2 domains) and with paxillin (via the COOH-terminal proline-rich domain), linking TCR signaling to the cytoskeleton. Co-immunoprecipitation, kinase activity assays, SH2 domain binding Journal of Experimental Medicine High 9091579
1997 Pyk2 is tyrosine-phosphorylated during an early, integrin-independent phase of platelet activation triggered by thrombin; phosphorylation is calcium-dependent, mediated through the PKC pathway, and requires actin cytoskeleton integrity. Pharmacological inhibition, antibody blocking, cytochalasin D treatment, immunoprecipitation Journal of Biological Chemistry High 9099753
1997 FcepsilonRI aggregation in mast cells activates Pyk2 downstream of Syk; calcium ionophore and PMA also activate Pyk2, and fibronectin adhesion dramatically enhances Pyk2 phosphorylation. G-protein-coupled receptor-induced Pyk2 phosphorylation is Syk-independent. Genetic epistasis (Syk-deficient cells), pharmacological stimulation, immunoprecipitation Journal of Biological Chemistry High 9405454
1998 CCR5 chemokine receptor (MIP-1beta) signals through RAFTK/Pyk2, leading to activation of paxillin and downstream JNK/SAPK and p38 MAPK; a dominant-negative kinase mutant of RAFTK markedly attenuated JNK/SAPK activity. Dominant-negative expression, kinase activity assays, co-immunoprecipitation Blood High 9446638
1998 Pyk2-H, a new isoform generated by alternative splicing, is expressed mainly in hematopoietic cells and is activated by TCR/BCR engagement and chemokines (RANTES, MIP-1beta); its C-terminus binds a different set of tyrosine-phosphorylated proteins than full-length Pyk2. Cloning, GST pulldown, immunoprecipitation, stimulation assays Journal of Biological Chemistry High 9603937
1998 In cardiac fibroblasts, angiotensin II activates Pyk2/CAKbeta in a Ca2+/calmodulin-sensitive manner, and Pyk2 mediates Ang II-induced Ras/ERK activation; dominant-negative Pyk2 significantly attenuated Ang II-induced ERK activity and GTP-Ras loading. Dominant-negative overexpression, RAS-GTP pull-down, kinase activity assays Hypertension High 9774361
1998 In osteoblastic cells, fluoroaluminate activates Pyk2 and induces its association with Src; Pyk2 binds the Src SH2 domain, and Src-associated Pyk2 shows >20-fold increased phosphorylation in kinase assays, indicating Src phosphorylates Pyk2. In vitro kinase assay, co-immunoprecipitation, SH2 domain binding Journal of Biological Chemistry High 9556630
1999 p130(Cas) and PYK2 form a stable complex in osteoclasts mediated by the SH3 domain of p130(Cas) and the C-terminal domain of PYK2; both proteins co-localize with F-actin, vinculin, and paxillin in the sealing zone and podosomes. Co-immunoprecipitation, domain mapping, immunofluorescence co-localization Journal of Biological Chemistry High 9988732
1999 RAFTK/Pyk2 activation (by dexamethasone) induces apoptosis in multiple myeloma cells; kinase-inactive RAFTK blocks Dex-induced apoptosis. IL-6 inhibits both RAFTK activation and Dex-induced apoptosis. Transient overexpression of wild-type and kinase-inactive mutants, apoptosis assays Oncogene High 10597281
2000 FIP200 (FAK family kinase-interacting protein of 200 kD) binds to the kinase domain of Pyk2, inhibits its kinase activity in vitro, suppresses Pyk2 activation and Pyk2-induced apoptosis in cells; biological stimulation of Pyk2 correlates with dissociation of the FIP200-Pyk2 complex. Yeast two-hybrid, in vitro kinase assay, co-immunoprecipitation, apoptosis assays Journal of Cell Biology High 10769033
2000 PYK2 localizes to podosomes in macrophages where it co-localizes with vinculin, talin, paxillin, and integrin alpha(M)beta(2); beta(2)-integrin ligation activates Pyk2 phosphorylation, and reduction of Pyk2 expression inhibits macrophage migration. Immunofluorescence co-localization, blocking antibodies, antisense knockdown, migration assays Cell Motility and the Cytoskeleton High 11056520
2000 Pyk2 and FAK associate with adhesion complexes containing EGF receptors through their carboxy- and amino-terminal domains; co-stimulation of growth factor receptors and integrins activates Pyk2/FAK and promotes neurite outgrowth, which requires Pyk2 autophosphorylation and its adhesion-targeting domain effectors such as paxillin. Co-immunoprecipitation, dominant-negative expression, domain deletion analysis, neurite outgrowth assays Nature Cell Biology High 10980697
2000 NGF induces RAFTK/Pyk2 phosphorylation in a Ca2+- and PLC-gamma-dependent manner; RAFTK translocates from cytoplasm to neurite initiation sites at the cell periphery, co-localizing with paxillin and actin, and is required for cytoskeletal organization in neurite formation. Pharmacological inhibition, confocal microscopy, co-immunoprecipitation Journal of Biological Chemistry High 10764815
2000 Pyk2 inhibits G1-to-S phase cell cycle progression (while FAK promotes it) by differentially activating JNK and suppressing ERK; the C-terminal domain of Pyk2 determines its cytoplasmic localization and association with Src/Fyn, key to these differential effects. Tetracycline-regulated expression, chimeric molecule analysis, JNK/ERK assays, FACS cell cycle analysis Journal of Cell Science High 10934044
2001 FAK inhibits PYK2 autophosphorylation and focal adhesion targeting via its N-terminus and FAT domain, respectively, and suppresses PYK2-mediated actin cytoskeleton reorganization and cell rounding. Microinjection, domain deletion analysis, immunofluorescence, kinase assays Journal of Cell Science High 11686301
2001 PYK2 links Gq-alpha and G13-alpha signaling to NF-kappaB activation via PI3K/Akt/IkappaB kinase cascade; kinase-dead PYK2 blocked NF-kappaB-dependent transcription and Akt activation induced by muscarinic receptor or G-alpha constructs. Dominant-negative expression, reporter gene assay, kinase inhibition, epistasis Journal of Biological Chemistry High 11435419
2001 In glomerular mesangial cells, ET-1 activates Pyk2 in a Src-dependent manner; dominant-negative Pyk2 (CRNK) inhibits ET-1-induced p38 MAPK (but not ERK) activation, placing Pyk2 upstream of p38 in this pathway. Adenoviral dominant-negative expression, phospho-specific antibodies, kinase activity assays Journal of Biological Chemistry High 11278444
2001 Pyk2 kinase activity is essential for pulmonary vascular endothelial cell spreading, migration, and morphogenesis/angiogenesis; Pyk2 kinase activity is required for expression of FAK, p130Cas, and HEF1, regulating focal adhesion formation and cytoskeletal reorganization. Adenoviral expression of Pyk2 mutants, cell spreading/migration assays, Western blotting Journal of Biological Chemistry High 11739395
2002 In cardiomyocytes, ET-1 activates a p130Cas/Crk/Pyk2/c-Src signaling complex (requiring Ca2+, PKC, actin cytoskeleton, and Src) that is selectively required for JNK activation but not ERK activation. Dominant-negative overexpression, co-immunoprecipitation, kinase activity assays, pharmacological inhibitors Hypertension High 12719447
2002 Pyk2 directly phosphorylates ARA55 at Tyr43, impairing ARA55 coactivator activity and suppressing androgen receptor transactivation; Pyk2 was isolated as an ARA55-interacting protein. Yeast two-hybrid, co-immunoprecipitation, in vitro phosphorylation, reporter assay Journal of Biological Chemistry High 11856738
2002 Pyk2/RAFTK activation induces tyrosine phosphorylation of alpha-synuclein at Tyr125 via Src-family kinases under hyperosmotic stress; Pyk2 lies upstream of Src-family kinases in this cascade. Overexpression, phosphorylation mapping, pharmacological inhibition FEBS Letters Medium 12096713
2003 Pyk2-/- macrophages fail to polarize, undergo membrane ruffling, or migrate in response to chemokines; they show impaired inositol trisphosphate production, Ca2+ release, Rho activation, and PI3K activation in response to integrin or chemokine stimulation. Homologous recombination knockout, chemotaxis assays, optical tweezers, Ca2+ imaging PNAS High 12960403
2004 RAFTK/Pyk2-mediated apoptosis in cardiomyocytes requires Src kinase activity; Tyr402 of RAFTK is the Src-binding site, and mutation of this site decreases DNA laddering. Paxillin (wild-type or phosphorylation-deficient mutant) prevents RAFTK-mediated apoptosis by interrupting signaling proximal but downstream of RAFTK. Adenoviral overexpression, site-directed mutagenesis, apoptosis assays, co-expression rescue Journal of Biological Chemistry High 15322113
2004 VEGF-induced p38 MAPK activation in endothelial cells requires RAFTK/Pyk2 (dominant-negative Pyk2 decreases p38 but not ERK activation) and is dependent on extracellular Ca2+; both Src and RAFTK/Pyk2 are essential for endothelial cell migration. Dominant-negative expression, pharmacological inhibition (EGTA), migration assays Oncogene High 14676843
2005 Pyk2 autophosphorylation is necessary but not sufficient for glioma cell migration; the N-terminal domain of Pyk2 is required for migration stimulation, whereas FAK's N-terminal domain substitution inhibits migration; RNA interference of Pyk2 significantly inhibits glioma migration. Domain-swapping chimeras, RNA interference, migration assays Neoplasia High 15967096
2008 Pyk2 physically interacts with mGluR1 and mGluR5; Pyk2 overexpression attenuates basal and agonist-stimulated inositol phosphate formation from mGluR1 by displacing Galphaq/11 from the receptor, while facilitating ERK1/2 phosphorylation downstream of mGluRs via Src-, calmodulin-, and PKC-dependent mechanisms. Co-immunoprecipitation, GST pulldown, inositol phosphate assay, ERK phosphorylation assay, dominant-negative expression Molecular Brain High 20180987
2008 alpha- and gamma-Protocadherins (PCDH-gamma and PCDH-alpha) bind PYK2 and FAK and inhibit their kinase activities; PYK2 activity is abnormally upregulated in Pcdh-gamma-deficient neurons, and overexpression of PYK2 induces neuronal apoptosis. Co-immunoprecipitation, kinase activity assay, Pcdh-gamma knockout neurons, overexpression in chick spinal cord Journal of Biological Chemistry High 19047047
2010 PSD-95 clusters and activates Pyk2 in neurons by promoting Pyk2 oligomerization, enabling trans-autophosphorylation at Tyr402; Ca2+ influx through NMDA receptors promotes Pyk2 interaction with PSD-95 in a Ca2+/calmodulin-dependent manner, and this mechanism is critical for LTP in hippocampal CA1. In vitro oligomerization assay, overexpression in PC6-3 cells, LTP electrophysiology, Ca2+ imaging Journal of Neuroscience High 20071509
2010 STEP (striatal-enriched protein-tyrosine phosphatase) directly binds and dephosphorylates Pyk2 at Tyr402; STEP KO mice show enhanced Pyk2 Tyr402 phosphorylation and downstream substrate phosphorylation (paxillin, ASAP1), and STEP blocks Pyk2 translocation to postsynaptic densities. In vitro phosphatase assay, co-immunoprecipitation, STEP KO mice, subcellular fractionation Journal of Biological Chemistry High 22544749
2010 Pyk2 nuclear localization is regulated by a nuclear export motif in the 700-841 linker region controlled by phosphorylation at Ser778 (a substrate of PKA and calcineurin); depolarization-induced Ca2+ influx causes calcineurin-dependent Ser778 dephosphorylation, enabling nuclear accumulation. Subcellular fractionation, site-directed mutagenesis, truncation analysis, transfected PC12 cells Cellular and Molecular Life Sciences High 22802128
2010 The Pyk2 FERM domain regulates Pyk2 activity by controlling Pyk2 oligomer formation; autonomous FERM domain fragments compete with full-length Pyk2 oligomerization and reduce Pyk2 phosphorylation; FERM deletion enhances Pyk2 complex formation and phosphorylation. Co-immunoprecipitation of differentially tagged Pyk2 constructs, domain deletion analysis Cellular Signalling High 20849950
2013 Pyk2 regulates platelet integrin alphaIIbbeta3 outside-in signaling; Pyk2-/- platelets show defective spreading on fibrinogen, reduced PI3Kbeta activation and Akt phosphorylation, and impaired Rap1b activation; Pyk2 activates c-Cbl tyrosine phosphorylation via p85-associated c-Cbl. Pyk2 knockout mice, platelet spreading assays, PI3K activity assay, co-immunoprecipitation Journal of Thrombosis and Haemostasis High 23216754
2013 MAP4K4 is identified as a Pyk2 FERM domain binding partner; MAP4K4 co-immunoprecipitates with Pyk2 and is a Pyk2 substrate; MAP4K4 and Pyk2 function together in glioma cell migration, with knockdown of either blocking the stimulatory effects of the other. Yeast two-hybrid, co-immunoprecipitation, kinase substrate assay, siRNA knockdown, migration assays Journal of Signal Transduction High 24163766
2015 FAK and PYK2 redundantly phosphorylate GSK3beta at Tyr216, reinforcing Wnt/beta-catenin signaling by promoting GSK3beta/beta-TrCP interaction and beta-catenin accumulation; pharmacological FAK/PYK2 inhibition suppresses adenoma formation in APCmin/+ mice. In vitro kinase assay, co-immunoprecipitation, mouse model (APCmin/+), pharmacological inhibition eLife High 26274564
2015 PYK2 translocates to early endosomes upon EGF stimulation, where it co-localizes with EGFR and sustains downstream signaling; PYK2 enhances EGF-induced STAT3 phosphorylation, and phospho-STAT3 directly binds the PYK2 promoter to upregulate PYK2 transcription, forming a positive feedback loop. Immunofluorescence/confocal microscopy, subcellular fractionation, chromatin immunoprecipitation, knockdown studies Nature Communications High 25648557
2016 Src kinase is required for the initial priming phosphorylation of Pyk2 at Tyr402 upon integrin (fibronectin) engagement; Src SH2 domain binds Pyk2, Y402 phosphorylation is a prerequisite for subsequent Y579 phosphorylation, and subsequent Pyk2 autophosphorylation in trans is required for full Pyk2 activation. Src inhibitors (pharmacological and genetic), SH2 domain mutants, phospho-specific Western blotting PLOS ONE High 26866924
2016 Pyk2 is phosphorylated by Syk upon NLRP3 inflammasome activation and relocalizes to ASC specks; Pyk2 (but not FAK) directly phosphorylates ASC at Tyr146, which is required for ASC oligomerization, speck formation, caspase-1 activation, and IL-1beta secretion. In vitro kinase assay, RNA interference, pharmacological inhibition, site-directed mutagenesis, ASC speck imaging Scientific Reports High 27796369
2017 Pyk2 colocalizes with cortactin at invadopodia of invasive breast cancer cells; Pyk2 directly phosphorylates cortactin and indirectly via Src-mediated Arg activation, driving actin polymerization in invadopodia, ECM degradation, and tumor invasion. Pyk2 regulates invadopodium-mediated functions while FAK controls focal adhesion-mediated motility. High-throughput protein array, co-immunoprecipitation, in vitro kinase assay, invadopodium assays, siRNA knockdown Journal of Cell Biology High 29133485
2018 Pyk2 is a direct tyrosine kinase for tau, phosphorylating it in vivo and in vitro; Pyk2 interacts with Fyn and its activity is regulated by Fyn (increased in FynCA mice, decreased in FynKO mice), placing Pyk2 downstream of Fyn in tau phosphorylation. In vitro kinase assay, co-immunoprecipitation, transgenic mouse models (FynCA, FynKO, Pyk2/tau double transgenic) Journal of Alzheimer's Disease High 29782321
2018 PYK2 positively regulates TAZ and YAP transcriptional activity in triple-negative breast cancer; PYK2 kinase activity is required to maintain TAZ protein stability by preventing its proteasomal degradation, and PYK2 enhances tyrosine phosphorylation of both TAZ and LATS1/2. siRNA knockdown, pharmacological inhibition, proteasome inhibitor rescue, Western blotting, tyrosine phosphorylation assays Cell Death & Disease High 30250159
2019 Pyk2 interacts with Graf1c (a RhoA GTPase-activating protein) in brain; Pyk2 inhibits Graf1c, thereby activating RhoA and reducing F-actin/dendritic spine density. Amyloid-beta oligomer-induced spine loss requires both Pyk2 kinase activity and RhoA activation. Biochemical isolation from brain, co-immunoprecipitation, dendritic spine imaging, pharmacological and genetic inhibition Journal of Neuroscience High 30626696
2020 CD56 (NCAM) stimulates Pyk2 phosphorylation at Tyr402 in NK cells; CD56 knockout reduces Pyk2 pY402, impairs lytic granule exocytosis and cytotoxicity during immunological synapse formation, and these defects are rescued by CD56 re-expression. CRISPR knockout, rescue expression, lytic granule exocytosis assay, cytotoxicity assay, immunological synapse imaging eLife High 32510326
2021 PTK2B/PYK2 directly phosphorylates IRF5; PYK2-deficient macrophages show impaired endogenous IRF5 activation and reduced inflammatory gene expression; PYK2 inhibitor defactinib mimics IRF5 deficiency transcriptionally and reduces colitis in mice and human colon biopsies. Kinase inhibitor library screening, PYK2 KO macrophages, transcriptomics, in vivo colitis model, human biopsy assays Nature Communications High 34795257
2021 PKM2 (pyruvate kinase M2) promotes Pyk2 activation downstream of TLR4, TLR7, and TLR9 signaling in macrophages, dendritic cells, and B cells, augmenting TLR pathway activation; PKM2 inhibition reduces Pyk2 phosphorylation and downstream inflammation. Overexpression, siRNA knockdown, pharmacological inhibition, Western blotting for Pyk2 phosphorylation Frontiers in Immunology Medium 34025679
2021 PTK2B/PYK2 directly phosphorylates TBK1 at Tyr591, increasing TBK1 oligomerization and activation; PTK2B also interacts with STING and promotes STING oligomerization in a kinase-independent manner, enhancing antiviral innate immune responses. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, Ptk2b-/- mice, viral infection assays Nature Communications High 37989995
2022 In PS19 tauopathy mice, endogenous Pyk2 suppresses tau phosphorylation and accumulation by inhibiting LKB1 and p38 MAPK activity; Pyk2 deletion worsens tau pathology, synapse loss, and spatial memory impairment. Pyk2 conditional knockout in PS19 mice, phospho-tau Western blotting, proteomics, behavioral testing Molecular Neurodegeneration High 35501917
2009 PYK2 directly interacts with MyD88 (via MyD88's death domain) in macrophages; PYK2-deficient macrophages show reduced IkappaB phosphorylation/degradation and decreased NF-kappaB activation and IL-1beta expression in response to LPS. Co-immunoprecipitation, PYK2-deficient macrophages, NF-kappaB reporter, domain deletion analysis Journal of Leukocyte Biology High 19955209
2016 Pyk2 is required for complement receptor 3 (CR3/integrin alphaM-beta2)-mediated phagocytosis but not FcgammaR-mediated phagocytosis in macrophages; Pyk2 is recruited to complement-opsonized bacteria, and CRISPR/Cas9 disruption of pyk2 impairs CR3-mediated uptake. siRNA knockdown, pharmacological inhibition, TAT-PRNK peptide, CRISPR/Cas9 KO, phagocytosis assays Journal of Innate Immunity High 26848986
2021 Structure-activity analysis of FAK/PYK2 inhibitors reveals that slowly dissociating FAK inhibitors induce helical structure at the DFG motif of FAK but not PYK2, providing a structural basis for kinetic selectivity; mutagenesis of DFG-helical residues confirms the hydrophobic interaction mechanism. High-resolution crystal structures, binding kinetics, mutagenesis, molecular simulation Cell Chemical Biology High 33497606
2001 RAFTK/Pyk2 co-immunoprecipitates with PI3K in activated platelets, and PI3K enzyme activity co-precipitates with RAFTK; at low thrombin doses, RAFTK phosphorylation and platelet aggregation are PI3K activity-dependent. SHP-2 (PTP-2) associates with RAFTK in a PI3K-dependent manner upon platelet activation. Co-immunoprecipitation, PI3K activity assay, pharmacological PI3K inhibition, platelet aggregation assay British Journal of Haematology Medium 11472358
2005 FAK and PYK2 interact with SAPAP3 (SAP90/PSD-95-associated protein-3) as shown by yeast two-hybrid and GST pulldown; all three proteins partly co-distribute with PSD-95 and Src in post-synaptic density fractions, suggesting SAPAP3 anchors FAK/PYK2 at synapses. Yeast two-hybrid, GST pulldown, sucrose gradient fractionation Biochemical and Biophysical Research Communications Medium 16202977
2000 T cell antigen receptor-induced IL-2 production requires Pyk2 Tyr402; Pyk2-Y402F mutant inhibits endogenous Pyk2 and reduces JNK and p38 MAPK (but not ERK) activation after TCR/CD28 co-ligation; Pyk2 associates with Zap70 and Vav when overexpressed. Stable transfection of kinase mutants, kinase activity assays, IL-2 ELISA, co-immunoprecipitation Journal of Biological Chemistry High 10867021

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
1996 Activation of Pyk2 by stress signals and coupling with JNK signaling pathway. Science (New York, N.Y.) 281 8670418
2003 Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration. Proceedings of the National Academy of Sciences of the United States of America 254 12960403
2000 Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins. Nature cell biology 182 10980697
1999 FAK and PYK2/CAKbeta in the nervous system: a link between neuronal activity, plasticity and survival? Trends in neurosciences 164 10354603
2005 The tyrosine kinase pyk2 promotes migration and invasion of glioma cells. Neoplasia (New York, N.Y.) 115 15967096
1998 Identification of a new Pyk2 isoform implicated in chemokine and antigen receptor signaling. The Journal of biological chemistry 113 9603937
1998 Beta-chemokine receptor CCR5 signals via the novel tyrosine kinase RAFTK. Blood 107 9446638
2015 FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β. eLife 106 26274564
1999 RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells. Oncogene 96 10597281
1999 Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone. The Journal of biological chemistry 92 9988732
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) 77 21132400
2016 Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis. Scientific reports 76 27796369
2000 PYK2 is an adhesion kinase in macrophages, localized in podosomes and activated by beta(2)-integrin ligation. Cell motility and the cytoskeleton 72 11056520
2008 alpha- and gamma-Protocadherins negatively regulate PYK2. The Journal of biological chemistry 71 19047047
2001 Inhibition of PYK2-induced actin cytoskeleton reorganization, PYK2 autophosphorylation and focal adhesion targeting by FAK. Journal of cell science 71 11686301
2012 Striatal-enriched protein-tyrosine phosphatase (STEP) regulates Pyk2 kinase activity. The Journal of biological chemistry 70 22544749
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
2000 Pyk2 and FAK differentially regulate progression of the cell cycle. Journal of cell science 69 10934044
2002 Role of EGF Receptor and Pyk2 in endothelin-1-induced ERK activation in rat cardiomyocytes. Journal of molecular and cellular cardiology 68 11851354
1994 Multiple tyrosine protein kinases in rat hippocampal neurons: isolation of Ptk-3, a receptor expressed in proliferative zones of the developing brain. Proceedings of the National Academy of Sciences of the United States of America 67 8127887
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 64 20071509
2018 CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer. Molecular cancer 63 29455640
2004 Expression of tyrosine kinases FAK and Pyk2 in 331 human astrocytomas. Acta neuropathologica 63 15221336
2005 PTK 787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors, represses tumor growth with high efficacy. Chembiochem : a European journal of chemical biology 61 15742376
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
2000 Cerebral ischemia and seizures induce tyrosine phosphorylation of PYK2 in neurons and microglial cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 10964954
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 Store-operated Ca(2+) entry regulates glioma cell migration and invasion via modulation of Pyk2 phosphorylation. Journal of experimental & clinical cancer research : CR 56 25433371
2017 Pyk2 and FAK differentially regulate invadopodia formation and function in breast cancer cells. The Journal of cell biology 55 29133485
2001 PYK2 links G(q)alpha and G(13)alpha signaling to NF-kappa B activation. The Journal of biological chemistry 54 11435419
2021 Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2. Cell chemical biology 53 33497606
2000 Characterization of the tyrosine kinases RAFTK/Pyk2 and FAK in nerve growth factor-induced neuronal differentiation. The Journal of biological chemistry 52 10764815
2004 Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kinase is antagonized by paxillin. The Journal of biological chemistry 50 15322113
2020 CD56 regulates human NK cell cytotoxicity through Pyk2. eLife 49 32510326
2003 Selective involvement of p130Cas/Crk/Pyk2/c-Src in endothelin-1-induced JNK activation. Hypertension (Dallas, Tex. : 1979) 47 12719447
1997 Activation of protein-tyrosine kinase Pyk2 is downstream of Syk in FcepsilonRI signaling. The Journal of biological chemistry 47 9405454
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
2001 Variations of proline-rich kinase Pyk2 expression correlate with prostate cancer progression. Laboratory investigation; a journal of technical methods and pathology 43 11204274
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 42 30626696
2011 Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition. PloS one 42 21533080
2018 Role of Pyk2 in Human Cancers. Medical science monitor : international medical journal of experimental and clinical research 41 30425234
2016 Novel Role of Src in Priming Pyk2 Phosphorylation. PloS one 40 26866924
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
2002 Calcitonin induces dephosphorylation of Pyk2 and phosphorylation of focal adhesion kinase in osteoclasts. Bone 38 12231407
2021 Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation. Frontiers in immunology 37 34025679
2018 Pyk2 is a Novel Tau Tyrosine Kinase that is Regulated by the Tyrosine Kinase Fyn. Journal of Alzheimer's disease : JAD 37 29782321
2015 Microglia Activate Migration of Glioma Cells through a Pyk2 Intracellular Pathway. PloS one 37 26098895
2007 The acid-activated signaling pathway: starting with Pyk2 and ending with increased NHE3 activity. Kidney international 37 17882150
2011 PYK2 signaling is required for PDGF-dependent vascular smooth muscle cell proliferation. American journal of physiology. Cell physiology 36 21451101
2010 Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation. Molecular brain 36 20180987
2008 Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation. Bioorganic & medicinal chemistry letters 35 18951788
2014 Adaptors for disorders of the brain? The cancer signaling proteins NEDD9, CASS4, and PTK2B in Alzheimer's disease. Oncoscience 34 25594051
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
2000 Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402. The Journal of biological chemistry 34 10867021
2015 PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop. Oncotarget 33 26084289
2013 The proline-rich tyrosine kinase Pyk2 regulates platelet integrin αIIbβ3 outside-in signaling. Journal of thrombosis and haemostasis : JTH 33 23216754
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 Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway. Journal of orthopaedic translation 32 35228997
2011 Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner. Experimental cell research 32 21640103
2018 PYK2 negatively regulates the Hippo pathway in TNBC by stabilizing TAZ protein. Cell death & disease 31 30250159
2007 Phospholipase C-gamma1 potentiates integrin-dependent cell spreading and migration through Pyk2/paxillin activation. Cellular signalling 31 17531443
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
2022 Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy. Molecular neurodegeneration 30 35501917
2011 Role of Pyk2 in cardiac arrhythmogenesis. American journal of physiology. Heart and circulatory physiology 30 21666110
2009 Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways. Journal of cellular biochemistry 30 19415692
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) 29 38247340
2003 Activation and nuclear translocation of PKCdelta, Pyk2 and ERK1/2 by gonadotropin releasing hormone in HEK293 cells. The Journal of steroid biochemistry and molecular biology 28 12943720
2010 The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation. Cellular signalling 27 20849950
1998 Fluoroaluminate induces activation and association of Src and Pyk2 tyrosine kinases in osteoblastic MC3T3-E1 cells. The Journal of biological chemistry 27 9556630
2021 Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation. Nature communications 26 34795257
1997 Characterization of the novel focal adhesion kinase RAFTK in hematopoietic cells. Leukemia & lymphoma 25 9402324
2012 PYK2: a calcium-sensitive protein tyrosine kinase activated in response to fertilization of the zebrafish oocyte. Developmental biology 24 23084926
2012 Pyk2 cytonuclear localization: mechanisms and regulation by serine dephosphorylation. Cellular and molecular life sciences : CMLS 23 22802128
2016 Spatial regulation of astral microtubule dynamics by Kif18B in PtK cells. Molecular biology of the cell 22 27559136
2013 A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration. Journal of signal transduction 22 24163766
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
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
2005 FAK and PYK2 interact with SAP90/PSD-95-Associated Protein-3. Biochemical and biophysical research communications 21 16202977
2023 PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling. Nature communications 20 37989995
2022 Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice. Frontiers in immunology 20 35178052