Affinage

PAK2

Serine/threonine-protein kinase PAK 2 · UniProt Q13177

Length
524 aa
Mass
58.0 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

PAK2 is a Rac1/Cdc42-activated serine/threonine kinase that integrates GTPase and stress signaling to control cytoskeletal dynamics, cell survival, and apoptosis, with its biological output determined by which of two mutually exclusive activation routes it takes (PMID:7744004, PMID:31926209). In the canonical route, GTP-loaded Rac1 or Cdc42 bind PAK2 via its CRIB motif and trigger autophosphorylation that activates the kinase and renders GTPase binding dispensable (PMID:7744004); autophosphorylation at Ser-141 then feeds back to reduce Cdc42 association and helps localize PAK2 to the endoplasmic reticulum, where ER targeting (dependent on Ser-490) is required for PAK2-induced cytostasis (PMID:12560339, PMID:16204230). The activated kinase remodels the actomyosin cytoskeleton through multiple substrates—inhibiting MLCK and monophosphorylating myosin II regulatory light chain (PMID:10748018, PMID:10639334), driving the LIMK1/cofilin axis (PMID:25824689, PMID:30134165), and negatively regulating RhoA by phosphorylating the exchange factor GEF-H1 (PMID:23204526, PMID:18411304). PAK2 acts within a betaPIX/GIT1 scaffold and at adherens junctions and focal adhesions to govern cell motility, polarity, and survival (PMID:16527308, PMID:19923322, PMID:22863318, PMID:31141452). In a second, proteolytic route, caspase-3 cleaves PAK2 to release a constitutively active, GTPase-independent C-terminal fragment (PAK2p34) that translocates to the nucleus and amplifies apoptotic morphological changes such as membrane blebbing (PMID:9171063, PMID:12853446); the two states function as a molecular switch, since Cdc42-activated full-length PAK2 is resistant to caspase cleavage and thereby pro-survival (PMID:31926209). PAK2 also globally tunes protein synthesis by phosphorylating eIF4G and Mnk1 to inhibit cap-dependent translation (PMID:16281055, PMID:15234964), and is essential for mouse embryonic development, T-cell and megakaryocyte differentiation, and the cardiac ER-stress/UPR response (PMID:21499899, PMID:24843022, PMID:25824689, PMID:30620686). A de novo human PAK2 nonsense mutation impairing PAK2 function, modeled by Pak2 haploinsufficiency in mice, causes synaptic and autism-related phenotypes (PMID:30134165). PAK2 is additionally exploited by HIV/SIV Nef, which selectively binds and activates PAK2 to inactivate cofilin and disrupt actin remodeling and TCR signaling in T cells (PMID:11070003, PMID:20147394, PMID:26350970).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 High

    Established how PAK2 is switched on, showing it is a direct GTPase effector whose activity, once triggered, becomes GTPase-independent.

    Evidence Recombinant binding and autophosphorylation/kinase assays with GTP-loaded Rac1/Cdc42 and MBP substrate

    PMID:7744004

    Open questions at the time
    • Did not define the downstream substrates engaged in cells
    • Structural basis of autoinhibition relief not resolved here
  2. 1997 High

    Revealed a second, proteolytic activation mode in which caspase-3 cleavage generates a constitutively active fragment driving apoptotic morphology.

    Evidence Caspase cleavage assay and dominant-negative PAK in Fas-induced Jurkat apoptosis

    PMID:9171063

    Open questions at the time
    • Did not establish nuclear targeting or turnover of the fragment
    • Substrates of the apoptotic fragment unidentified
  3. 2000 High

    Connected PAK2 activity to actomyosin contractility by identifying MLCK and myosin II as effectors controlling endothelial tension and cytoskeletal rearrangement.

    Evidence In vitro kinase assays with site mapping, microinjection, co-IP, and permeabilized endothelial tension assays

    PMID:10639334 PMID:10748018

    Open questions at the time
    • In vivo relevance to vascular barrier function not established
    • Regulation of substrate choice (MLCK vs myosin II) unclear
  4. 2000 High

    Placed PAK2 within cell-cycle control, showing reciprocal regulation with MPF during oocyte maturation.

    Evidence Xenopus oocyte maturation with dominant-negative GTPases and in vitro MPF phosphorylation of PAK2

    PMID:10644687

    Open questions at the time
    • MPF phosphorylation sites on PAK2 not mapped
    • Mammalian conservation of this feedback not addressed here
  5. 2003 High

    Defined the structural/localization logic of the two PAK2 states: full-length kinase at the ER drives cytostasis, while caspase cleavage exposes an NLS allowing nuclear translocation and proteasome-regulated apoptotic activity.

    Evidence Subcellular fractionation, NLS/NES and Ser-490 mutagenesis, proteasome inhibition, ionizing-radiation cytostasis model

    PMID:12560339 PMID:12853446

    Open questions at the time
    • Mechanism of ER tethering at the molecular level unresolved
    • E3 ligase mediating PAK2p34 ubiquitination not identified
  6. 2002 High

    Showed PAK2 activity is fine-tuned beyond GTPases, with tyrosine phosphorylation at Y130 superactivating GTPase-primed PAK2 and ERK coupling it to growth-factor signaling.

    Evidence Src/pervanadate treatment, PP1 inhibition, Y130 mutagenesis, ERK co-IP and betaPIX phosphorylation in PC12 cells

    PMID:12215529 PMID:12226077

    Open questions at the time
    • Identity of the physiological tyrosine kinase in vivo not fixed
    • Integration of Y130 with autophosphorylation events unclear
  7. 2003 High

    Provided rigorous enzymology, defining PAK2's random bi-bi catalytic mechanism and distinguishing it from PKA.

    Evidence Steady-state kinetics and viscosity-variation analysis with MBP and LIMKtide substrates

    PMID:12549935

    Open questions at the time
    • Kinetics of physiological substrates beyond MBP/LIMKtide not measured
  8. 2004 High

    Linked PAK2 to translational control during apoptosis through Mnk1 phosphorylation, and revealed isoform-specific behavior of the caspase-cleaved fragment.

    Evidence In vitro kinase assays, phosphopeptide mapping, Edman degradation in H2O2-treated 293T cells

    PMID:15234964

    Open questions at the time
    • Quantitative contribution to global translation suppression in vivo not established
  9. 2004 Medium

    Identified an inhibitory mechanism for the apoptotic fragment, with PS-GAP binding PAK2p34 to suppress its kinase activity and redirect its localization.

    Evidence Co-IP, kinase activity, immunofluorescence, and cell death assays

    PMID:15471851

    Open questions at the time
    • Limited mechanistic depth; binding interface not mapped
    • Physiological setting where PS-GAP restrains apoptosis unclear
  10. 2005 High

    Extended PAK2 control of translation to homeostatic cap-dependent initiation, showing it phosphorylates eIF4G to compete out eIF4E under hyperosmotic stress, and identified Ser-141 autophosphorylation as a Cdc42-binding rheostat.

    Evidence In vitro kinase assays, m7GTP pulldowns, reticulocyte reconstitution, RNAi, and Ser-141 GST-pulldown analysis

    PMID:16204230 PMID:16281055

    Open questions at the time
    • Stimuli selecting translational vs cytoskeletal output not defined
    • Interplay of Ser-141 with ER localization mechanistically incomplete
  11. 2006 High

    Established PAK2 as a regulator of oncogenic and adhesion signaling through Myc, c-Abl, and a high-resolution betaPIX SH3 interaction, and resolved membrane targeting of the apoptotic fragment by myristoylation.

    Evidence In vitro kinase/binding assays with site mutagenesis, crystallography of betaPIX SH3-PAK2 peptide, and myristoylation/localization assays

    PMID:14749374 PMID:16527308 PMID:16617111 PMID:18161990

    Open questions at the time
    • In vivo relevance of Myc and c-Abl phosphorylation to tumorigenesis not tested
    • How myristoylation is enzymatically installed post-cleavage unresolved
  12. 2009 High

    Defined PAK2 scaffolding and its contextual regulation, including the betaPIX/GIT1/MYO18A motility complex, Erbin/Merlin-controlled activation, and huntingtin-mediated protection from caspase cleavage.

    Evidence Proteomic co-IP, in vitro binding, kinase activity, knockdown rescue, and in vitro caspase cleavage assays

    PMID:19240112 PMID:19289088 PMID:19923322

    Open questions at the time
    • Direct vs indirect nature of some interactions partly inferred from co-IP
    • Tissue-specific deployment of these regulators not mapped
  13. 2011 High

    Genetically separated PAK2's essential and apoptotic functions, showing full-length PAK2 is required for embryogenesis while caspase-generated PAK2p34 is dispensable for viability but amplifies apoptosis.

    Evidence PAK2 knockout and caspase-cleavage-deficient D212N knock-in mice with MEF cell death and effector caspase assays

    PMID:21499899

    Open questions at the time
    • Developmental process requiring PAK2 not pinpointed
    • Tissue contexts where the apoptotic amplifier is decisive unclear
  14. 2012 High

    Detailed PAK2's antagonism of TGF-beta/Smad and RhoA signaling and its survival role at junctions, including GEF-H1 and Smad2 phosphorylation and Scrib/betaPIX recruitment.

    Evidence Conditional KO, in vitro kinase assays with site mutagenesis, co-IP, RhoA pulldowns, and anoikis/degranulation assays

    PMID:22393057 PMID:22863318 PMID:23171552 PMID:23204526

    Open questions at the time
    • Some site assignments (e.g., Ser-20) not fully validated by mutagenesis
    • How PAK2 chooses pro-survival vs pro-apoptotic output at junctions unresolved
  15. 2014 High

    Demonstrated PAK2's developmental and cell-cycle roles in vivo, being required for thymocyte development via actin-dependent TCR signaling and for Rac1-dependent centrosomal mitotic entry.

    Evidence T-cell-specific conditional KO with TCR signaling/actin assays and centrosome fractionation with Rac1 inhibition

    PMID:24840740 PMID:24843022

    Open questions at the time
    • Centrosomal substrates of PAK2 not biochemically defined (Medium-confidence)
    • Direct PAK2 targets linking actin to PLCgamma1/Erk not all mapped
  16. 2015 High

    Expanded PAK2 biology to megakaryopoiesis and non-canonical activation, showing it drives cytoskeletal/endomitosis control in megakaryocytes and is activated downstream of TSC/RHEB independent of mTOR.

    Evidence Conditional KO megakaryocyte studies with LIMK1/cofilin/Aurora phospho-assays, and kinome profiling in Tsc2-/- MEFs

    PMID:25824689 PMID:26412398

    Open questions at the time
    • Biochemical mechanism of RHEB-to-PAK2 activation unresolved (Medium-confidence)
    • How PAK2 coordinates endomitosis vs proplatelet formation unclear
  17. 2016 High

    Showed PAK2 directly restrains apoptosis by phosphorylating caspase-7 at two sites through distinct allosteric and substrate-blocking mechanisms, and links to angiogenic polarity via paxillin.

    Evidence Structural and in vitro kinase analysis with caspase-7 site mutagenesis, and siRNA/co-IP polarity-complex studies in endothelial cells

    PMID:27889207 PMID:31141452

    Open questions at the time
    • Cellular conditions favoring caspase-7 inhibition vs caspase-3 cleavage of PAK2 not integrated
    • Par3-PAK2-paxillin complex assembly partly inferred from co-IP (Medium)
  18. 2018 High

    Tied PAK2 to human neurodevelopmental disease and to upstream oncogenic kinases, with haploinsufficiency causing synaptic/autism phenotypes and CDK12 phosphorylating PAK2 to drive MAPK signaling in cancer.

    Evidence Pak2+/- mice with LTP/behavior and a human nonsense mutation; co-IP, MS, in vitro kinase assays and xenografts for CDK12

    PMID:30134165 PMID:32483448

    Open questions at the time
    • Precise synaptic substrate repertoire beyond LIMK1/cofilin incomplete
    • CDK12-PAK2 generality across tumor types not established (Medium)
  19. 2019 High

    Defined PAK2's protective role in cardiac ER-stress responses and force-dependent survival/apoptosis decisions, plus a role in senescence chromatin regulation.

    Evidence Cardiac-specific conditional KO with IRE-1/XBP-1/PP2A analysis and rescue; E-cadherin force application with AMPK binding and cleavage-resistant mutants; siRNA/overexpression with H3.3/HIRA assays and progeroid mice

    PMID:30620686 PMID:30940647 PMID:31209047

    Open questions at the time
    • Direct PAK2 substrate in the UPR pathway not fully defined
    • How force amplitude is converted into cleavage decision mechanistically incomplete
  20. 2020 High

    Crystallized the cytostasis/apoptosis switch by showing Cdc42-activated full-length PAK2 is refractory to caspase-3 cleavage, defining two mutually exclusive states.

    Evidence In vitro caspase-3 cleavage assays comparing Cdc42-activated vs full-length PAK2 with H2O2 cell death readouts

    PMID:31926209

    Open questions at the time
    • Structural basis of cleavage resistance not resolved
    • In vivo prevalence of each state under physiological stress unknown
  21. 2023 High

    Identified a PAK2-septin cascade controlling regulated exocytosis, required for von Willebrand factor release and platelet-string formation.

    Evidence APEX2 proximity labeling, dual loss-of-function screen, co-IP, and genetic/pharmacological PAK2 inhibition with VWF release assays

    PMID:36564030

    Open questions at the time
    • Direct septin substrate/binding partner of PAK2 not defined
    • Whether kinase activity vs scaffolding drives septin ring formation unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single kinase's localization, autophosphorylation state, and upstream input (GTPase, RHEB, CDK12, tyrosine kinases, mechanical force) are integrated to deterministically select among PAK2's opposing outputs—cytostasis, survival, translational shutdown, and apoptosis.
  • No unifying model predicting output from input/localization
  • Structural transitions between full-length states not fully mapped
  • In vivo substrate hierarchy across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0060089 molecular transducer activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 6 R-HSA-162582 Signal Transduction 5 R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-109582 Hemostasis 2 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2
Partners
CDC42ERKGIT1HSP90MYO18ANCKPAK1IP/BETAPIXSYK
Complex memberships
PAK2-septin ringPar3-PAK2-paxillin polarity complexbetaPIX/GIT1 complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 During apoptosis, caspase-3 proteolytically cleaves PAK2 between its N-terminal regulatory domain and C-terminal catalytic domain, generating a constitutively active PAK2 fragment that is GTPase-independent and regulates apoptotic morphological changes (membrane blebbing, phosphatidylserine externalization). Dominant-negative PAK mutant-expressing Jurkat cells were resistant to Fas-induced apoptotic body formation. Caspase cleavage assay, dominant-negative stable cell lines, Fas-induced apoptosis in Jurkat T cells Science High 9171063
1995 PAK2 (hPAK65) binds Rac1 and Cdc42 in a GTP-dependent manner, and GTP-bound Rac1/Cdc42 induces PAK2 autophosphorylation on serine residues, which stimulates its kinase activity toward myelin basic protein. Once activated, Rac1/Cdc42 are no longer required to maintain PAK2 activity. Protein purification from neutrophil cytosol, peptide sequencing, recombinant protein binding assays, autophosphorylation assays, kinase assays with MBP The EMBO journal High 7744004
2000 PAK2 phosphorylates myosin light chain kinase (MLCK) at Ser-439 and Ser-991, inhibiting MLCK activity and thereby reducing myosin II regulatory light chain phosphorylation. This blunts isometric tension development by ~75% in permeabilized endothelial monolayers. Calmodulin binding to MLCK blocks PAK2 phosphorylation of Ser-991. In vitro kinase assay with Cdc42-activated and recombinant constitutively active PAK2, site-directed mutagenesis identification of phosphorylation sites, permeabilized endothelial monolayer tension assay The Journal of biological chemistry High 10748018
2000 PAK2 directly associates with myosin II and monophosphorylates the myosin II regulatory light chain, inducing retraction of endothelial cell margins and cytoskeletal rearrangement. This effect is dependent on myosin ATPase activity but not on MLCK. Microinjection of constitutively active PAK2, selective kinase inhibitors (staurosporine, BDM, KT5926), co-immunoprecipitation of endogenous PAK2 with myosin II Journal of cell science High 10639334
2002 PAK2 phosphorylates p85 betaPIX at Ser-525 and Thr-526 downstream of the Ras/ERK pathway. PAK2 directly binds ERK, and ERK-dependent PAK2 activation is required for bFGF-induced betaPIX translocation to lamellipodia at neuronal growth cones and subsequent neurite outgrowth. Metabolic labeling, gel mobility shift, MEK inhibitor (PD98059), co-IP of PAK2 with ERK, phosphorylation site mutagenesis (S525A/T526A), PC12 cell transfection The Journal of biological chemistry High 12226077
2003 TGF-β receptor signaling activates PAK2 in fibroblasts but not epithelial cells, in a Rac1/Cdc42-dependent, Smad2/Smad3-independent manner. Dominant-negative PAK2 or PAK2 morpholino antisense oligonucleotides prevent TGF-β-induced fibroblast morphological transformation. Kinase activity assays, dominant-negative PAK2, morpholino antisense oligonucleotides, Smad2/3 knockout/knockdown, Rac1/Cdc42 inhibition Molecular and cellular biology High 14612425
2004 PAK2 phosphorylates the Myc oncoprotein at three sites (T358, S373, T400). Phosphorylation at S373 and T400 blocks Myc-Max dimerization; phosphorylation at T358 directly interferes with Myc-DNA binding. This inhibits Myc-driven transcription, proliferation, transformation of NIH 3T3 cells, and apoptosis on serum withdrawal. In vitro kinase assay, mutagenesis of phosphorylation sites, transcription assays, NIH 3T3 transformation assay, serum withdrawal apoptosis assay Molecular and cellular biology High 14749374
2003 Full-length PAK2 localizes to the cytoplasm; caspase-3 cleavage removes the regulatory domain including the nuclear export signal (NES), allowing the C-terminal PAK2p34 fragment to translocate to the nucleus via a nuclear localization signal. Nuclear PAK2p34 is ubiquitinated and degraded by the 26S proteasome; blocking its polyubiquitination markedly increases PAK2p34 levels and stimulates apoptosis. Immunofluorescence localization, subcellular fractionation, NLS/NES mutagenesis, proteasome inhibitor treatment, polyubiquitination assays The Journal of biological chemistry High 12853446
2003 PAK2 (gamma-PAK) localizes to the endoplasmic reticulum (ER) in a manner dependent on Ser-490; ER localization is required for PAK2-induced cytostasis. Kinase-inactive and Ser-490 phosphomimetic mutants fail to localize to the ER and do not inhibit cell division. Immunofluorescence, sucrose density gradient centrifugation/fractionation, site-directed mutagenesis (S490A, S490D), ionizing radiation-induced cytostasis model The Journal of biological chemistry High 12560339
2005 PAK2 binds to and phosphorylates eIF4G, competing with eIF4E for the same binding region on eIF4G. Phosphorylation of eIF4G at S896 inhibits its association with eIF4E (m7GTP cap-binding), reducing cap-dependent translation initiation. Activation of PAK2 by hyperosmotic stress inhibits cap-dependent but not IRES-driven translation. In vitro kinase assay, co-immunoprecipitation, m7GTP-sepharose pulldown, reticulocyte lysate reconstitution with phosphorylated eIF4G, RNAi knockdown, eIF4G mutagenesis (S896A/D) The EMBO journal High 16281055
2004 Caspase-cleaved PAK2 (but not Cdc42-activated full-length PAK2) phosphorylates Mnk1 at Thr-22 and Ser-27. This phosphorylation does not activate Mnk1 toward eIF4E but inhibits Mnk1-mediated phosphorylation of eIF4G by up to 50% and reduces binding of eIF4G peptides to Mnk1 by up to 80%, providing a mechanism for translational inhibition during apoptosis. In vitro kinase assay, 2D tryptic phosphopeptide mapping, automated/manual Edman degradation, kinetic analysis, 293T cell apoptosis (hydrogen peroxide) The Journal of biological chemistry High 15234964
2006 Caspase-cleaved PAK2 C-terminal kinase fragment (C-t-PAK2) undergoes posttranslational myristoylation. This myristoylation, together with an adjacent polybasic domain, directs C-t-PAK2 to membrane ruffles and internal membranes. Abolishing myristoylation significantly reduces both membrane localization and cell death-promoting activity of C-t-PAK2, and proper myristoylation increases JNK signaling. Myristoylation assay, EGFP fusion localization, mutagenesis of myristoylation site, cell death assays, JNK pathway analysis Proceedings of the National Academy of Sciences of the United States of America High 16617111
2000 HIV-1 and SIV Nef specifically activates PAK2 (not PAK1). Ectopically expressed PAK2 substitutes for Nef-associated kinase (Nak), while PAK1 cannot. Nef mediates robust activation of PAK2; most active PAK2 is bound to Nef but only a small fraction of total Nef is PAK2-associated. Caspase 3 cleavage sensitivity assay (distinguishing PAK2 from PAK1), ectopic expression, co-immunoprecipitation, kinase assays in multiple cell lines Journal of virology High 11070003
2001 HIV-1 Nef selectively associates with PAK2 but not PAK1. The selective interaction maps to the carboxy-terminal part of PAK2's regulatory domain. An intact CRIB (Cdc42-Rac1 interactive binding) motif in PAK2 is required for Nef-PAK2 complex formation; Nck or betaPIX binding to PAK2 is dispensable. Nef-associated PAK2 represents a minor subpopulation with distinctively high specific kinase activity. PAK1/PAK2 chimeric protein exchange mapping, co-immunoprecipitation, kinase activity assays, site mutagenesis Journal of virology High 11160719
2002 GTPase-mediated activation of PAK2 can be potentiated by cellular tyrosine kinases via phosphorylation of PAK2 at Y130 in its N-terminal regulatory domain. This tyrosine phosphorylation-mediated superactivation requires prior GTPase-induced conformational change (not catalytic activation per se) and can be blocked by Src inhibitor PP1 or Y130 mutation. Src overexpression, pervanadate treatment, PP1 inhibition, PAK2 mutagenesis (Y130), kinase activity assays, autoinhibitory domain mutant analysis Molecular and cellular biology High 12215529
2005 PAK2 autophosphorylation at Ser-141 (in the regulatory domain) is required for optimal kinase activity and negatively regulates PAK2 interaction with Cdc42(GTP). S141A mutant retains 6-fold higher Cdc42 binding than S141D, and S141A reduces autophosphorylation and substrate phosphorylation by ~45%. Binding of Cdc42 localizes PAK2 to the ER, where autophosphorylation at Ser-141 then reduces Cdc42 association. Site-directed mutagenesis (S141A, S141D, S165A, S165D), GST pulldown with Cdc42(GTP), autophosphorylation assays, 293T cell transfection, ER localization The Journal of biological chemistry High 16204230
2004 PAK2 physically interacts with Syk tyrosine kinase; Pak2 phosphorylates and activates Syk in vitro. Cdc42 enhances PAK2-Syk association. Under hyperosmotic stress, PAK2 and Syk co-translocate to the perinuclear region. PAK2 siRNA suppresses sorbitol-induced Syk and JNK activation, identifying a Cdc42→PAK2→Syk→JNK pathway. Co-transfection/co-immunoprecipitation in COS cells, in vitro kinase assay, PAK2 siRNA, immunofluorescence localization, JNK activity assay Molecular and cellular biology High 14673144
2006 PAK2 phosphorylates c-Abl at Ser-637 and Ser-638, which are adjacent to the PxxP motif that binds the Abi2 SH3 domain. This phosphorylation reduces Abi2 binding to c-Abl by ~90% and increases Crk binding to c-Abl 2-fold, thereby altering c-Abl substrate interactions. The phosphomimetic c-Abl 3D mutant also shows increased tyrosine kinase activity. In vitro kinase assay with PAK2, site-directed mutagenesis (3A, 3D), GST pulldown, Abi2 and Crk binding assays, tyrosine kinase activity assay Biochemistry High 18161990
2006 TGF-β activates c-Abl kinase in fibroblasts in a PAK2-dependent manner. PAK2 inhibition (dominant-negative or pharmacological) prevents TGF-β-induced c-Abl activation, placing PAK2 upstream of c-Abl in a PI3K-dependent, Smad-independent, receptor internalization-independent pathway. Dominant-negative PAK2, PI3K inhibitors, c-Abl kinase assays, TGF-β receptor signaling assays The Journal of biological chemistry Medium 16867995
2006 Crystal structure of the betaPIX SH3 domain in complex with a high-affinity PAK2 peptide (PxxxPR motif) solved at 1.3 Å resolution. The arginine of the PxxxPR motif forms a salt bridge with SH3 domain residues as the key determinant of high-affinity binding. C-terminal residues engage RT-loop for additional specificity. X-ray crystallography at 0.92 Å (SH3 alone) and 1.3 Å (complex), structural analysis Journal of molecular biology High 16527308
2008 PAK2 depletion (siRNA) in breast carcinoma cells enhances myosin light chain (MLC) phosphorylation (opposite to PAK1 depletion which decreases it), increases focal adhesion size, and enhances RhoA activity. Inhibiting RhoA signaling in PAK2-depleted cells decreases MLC phosphorylation and restores invasion, placing PAK2 as a negative regulator of RhoA→MLC phosphorylation. siRNA knockdown, phospho-MLC immunoblot, focal adhesion immunofluorescence, RhoA activity assay, Rho inhibitor rescue, transwell invasion assay Molecular and cellular biology High 18411304
2008 Conformational analysis by amide hydrogen/deuterium exchange mass spectrometry revealed that caspase-3 cleavage of PAK2 produces structural changes in the autoinhibitory domain (AID) and upper catalytic lobe, relaxing allosteric inhibition. ATP binding induces minor changes; autophosphorylation at Ser-141 and Thr-402 further increases solvent accessibility at the AID/G-helix interface, generating an expanded, more dynamic active enzyme. H/D exchange coupled with mass spectrometry (HDXMS), gel filtration, caspase-3 cleavage, autophosphorylation The Journal of biological chemistry High 18984590
2009 PAK2 forms a complex with betaPIX and GIT1; MYO18A is a novel PAK2 binding partner that binds through the betaPIX/GIT1 complex (not directly to PAK2). MYO18A knockdown does not disrupt PAK2/betaPIX/GIT1 complex but redirects it from lamellipodia to focal adhesions, reducing cell motility. Proteomic co-IP, siRNA knockdown, in vitro binding assay, colocalization by immunofluorescence, migration assay with reexpression rescue Molecular biology of the cell High 19923322
2009 The epithelial protein Erbin controls NF2 tumor suppressor Merlin function by determining the output of Merlin's interaction with PAK2. In mesenchymal cells (lacking Erbin), TGF-β–activated PAK2 inhibits Merlin. In epithelial cells, Erbin/Merlin complexes bind and inactivate GTPase-bound PAK2, preventing inappropriate PAK2 activation. Co-immunoprecipitation, PAK2 kinase activity assays, Erbin and Merlin knockdown/overexpression, cell-type comparison Developmental cell High 19289088
2009 Huntingtin interacts with PAK2 and inhibits caspase-3- and caspase-8-mediated cleavage of PAK2, both in cells and in vitro. Huntingtin overexpression is cytoprotective against TNFα, but this protection is lost upon PAK2 knockdown, demonstrating that huntingtin's anti-apoptotic function requires PAK2. Co-immunoprecipitation, in vitro caspase cleavage assay, PAK2 knockdown, TNFα-induced apoptosis assay Journal of cell science High 19240112
2010 PAK2 binds and phosphorylates c-Jun at five threonine sites (Thr2, Thr8, Thr89, Thr93, Thr286) in vitro and in cells. PAK2 knockdown reduces EGF-induced AP-1 activity and anchorage-independent transformation; mutation of all five PAK2 phosphorylation sites in c-Jun decreases JB6 cell transformation. In vitro kinase assay, co-IP, site mutagenesis, PAK2 siRNA knockdown, AP-1 reporter assay, soft agar transformation assay Carcinogenesis High 21177766
2012 PAK2 (but not PAK1) negatively regulates RhoA in mast cells by phosphorylating guanine nucleotide exchange factor GEF-H1 at an inhibitory site, which increases GEF-H1 microtubule binding and reduces RhoA stimulation. PAK2 loss induces increased antigen-mediated adhesion, degranulation, and cytokine secretion, reversed by Rho-specific inhibitor. Pak2 conditional knockout, kinase assay, GEF-H1 phosphorylation/microtubule binding assay, RhoA-GTP pull-down, degranulation assay, Rho inhibitor rescue The Journal of biological chemistry High 23204526
2012 PAK2 phosphorylates Smad2 at Ser-417, which is adjacent to the L3 loop mediating TβRI-Smad2 interaction. Substitution S417E attenuates Smad2-TβRI association. PAK2 associates with Smad2/3 in a kinase activity-dependent manner, blocking receptor-mediated Smad2/3 phosphorylation and TGF-β transcriptional responsiveness in MDCK epithelial cells. In vitro kinase assay, site mutagenesis (S417E), co-immunoprecipitation, TGF-β reporter assay, PAK2 knockdown The Journal of biological chemistry High 22393057
2012 PAK2 is recruited to adherens junctions via Scrib and betaPIX. At adherens junctions, the betaPIX-PAK2 complex counterbalances Scrib-mediated apoptotic signaling and cadherin-induced anoikis. PAK2 loss sensitizes cells to anoikis and osmotic stress-induced cell death. siRNA knockdown, co-immunoprecipitation, cell survival/anoikis assays, osmotic stress assay, adherens junction localization by immunofluorescence Current biology Medium 22863318
2012 Nitric oxide (NO) production by protein kinase A (PKA) in endothelial cells on basement membrane phosphorylates PAK2 at Ser-20 in its Nck-binding domain, blocking PAK2 membrane recruitment by preventing interaction with the adaptor protein Nck. This reduces PAK2/NF-κB activation and proinflammatory gene expression under shear stress. Co-immunoprecipitation of PAK2 with Nck, shear stress model, PKA inhibition, NO measurement, NF-κB reporter, ICAM-1 expression, Ser-20 phosphorylation analysis Molecular biology of the cell Medium 23171552
2014 T-cell-specific deletion of Pak2 in mice causes severe T cell lymphopenia with defects in pre-TCR β-selection and positive selection. Pak2 is required for TCR-triggered actin cytoskeletal remodeling; its loss impairs PLCγ1 and Erk1/2 signaling, linking actin cytoskeleton-dependent signaling to thymocyte development. Pak2-deficient CD4+ SP thymocytes show reduced S1P1 and KLF2 expression, impairing egress. T-cell-specific conditional Pak2 knockout mice, flow cytometry, TCR signaling assays (PLCγ1, Erk1/2 phosphorylation), actin polymerization assays, S1P1/KLF2 expression analysis eLife High 24843022
2015 Pak2 loss in megakaryocytes leads to macrothrombocytopenia and increased polyploidization (endomitosis). Pak2-deficient megakaryocytes show decreased phosphorylation of LIMK1, cofilin, and Aurora A/B/C, altered β1-tubulin expression and organization, and reduced proplatelet formation, establishing Pak2 as a regulator of endomitosis and cytoskeletal dynamics in megakaryopoiesis. Conditional Pak2 knockout mice, megakaryocyte differentiation in vitro, phosphorylation assays (LIMK1, cofilin, Aurora kinases), β1-tubulin immunofluorescence, ploidy analysis, proplatelet extension assay Blood High 25824689
2015 PAK2 is an effector downstream of TSC1/2-RHEB signaling independent of mTOR and p21RAC. In Tsc2-/- MEFs, PAK2 is overactivated via RHEB and is responsible for the migratory and cell cycle abnormalities observed. RHEB mediates PAK2 activation in a manner distinct from the canonical GTPase-PAK2 pathway. Kinome profiling, Tsc2-/- MEFs, RHEB manipulation, mTOR inhibitor treatment, PAK2 kinase assay, migration and cell cycle assays Scientific reports Medium 26412398
2016 PAK2 directly phosphorylates caspase-7 at two sites: S30 and S239. S30 phosphorylation allosterically blocks caspase-9-mediated processing of caspase-7 (preventing activation), while S239 phosphorylation in active caspase-7 prevents substrate binding. Both mechanisms are distinct and block apoptosis at different stages. Structural analysis, in vitro kinase assay, mutagenesis of S30 and S239, caspase-9 processing assay, substrate binding assay Structure High 27889207
2003 Kinetic analysis of PAK2 phosphorylation of protein substrate MBP follows a rapid-equilibrium random bi-bi mechanism, with kcat partially rate-limited by both phosphoryl transfer (31 s-1) and product release (19 s-1). For peptide substrate LIMKtide, product release (86 s-1) is faster than phosphoryl transfer (19 s-1), differing from cAMP-dependent kinase catalytic mechanism. Steady-state kinetics, viscosity variation experiments with sucrose, substrate variation analysis Biochemistry High 12549935
2000 In Xenopus oocytes, Cdc42 (but not Rac1) is required to maintain X-PAK2 in an active state in resting oocytes. During meiotic maturation, MPF (cyclin B-p34cdc2) phosphorylates and inactivates X-PAK2, establishing a positive feedback loop where PAK2 inactivation permits MPF amplification and maturation to proceed. Xenopus oocyte maturation model, dominant-negative Rac1 and Cdc42, purified active MPF in vitro kinase assay on PAK2, in-oocyte PAK2 activation assay The Journal of biological chemistry High 10644687
2010 Lentiviral Nef proteins from HIV-1, HIV-2, and SIV exploit PAK2 to deregulate cofilin and inhibit chemokine-induced actin remodeling in T lymphocytes. Even Nef variants with low in vitro PAK2-binding affinity require an intact PAK2 recruitment motif and endogenous PAK2 for this function, demonstrating PAK2-mediated cofilin inactivation as a broadly conserved Nef mechanism. Analysis of 17 lentiviral Nef proteins, PAK2 recruitment motif mutagenesis, cofilin phosphorylation assay, actin remodeling assay, T lymphocyte chemotaxis assay Journal of virology High 20147394
2015 HIV-1 Nef exploits PAK2 in a stepwise mechanism: PAK2 kinase activity phosphorylates/inactivates cofilin directly, while PAK2 also serves as a structural adaptor (independent of its catalytic activity) for recruiting the exocyst complex (EXOC) to Nef. PAK2-EXOC cooperate specifically to inhibit actin remodeling and proximal TCR signaling. Co-immunoprecipitation in HIV-infected T lymphocytes, PAK2 catalytic mutants, EXOC knockdown, actin remodeling assay, TCR signaling assay mBio High 26350970
2018 PAK2 haploinsufficiency in mice reduces phosphorylation of LIMK1 and cofilin, impairs actin polymerization at synapses, reduces synapse density, and causes defective long-term potentiation and autism-related behaviors. A de novo human PAK2 nonsense mutation similarly impairs PAK2 function in vitro and in vivo. Pak2+/- mice, phospho-LIMK1/cofilin immunoblot, actin polymerization assay, electrophysiology (LTP), behavioral testing, human nonsense mutation functional analysis Cell reports High 30134165
2019 PAK2 localizes in close proximity to the ER membrane in cardiomyocytes and is required for protective ER stress response via the IRE-1/XBP-1-dependent unfolded protein response pathway. PAK2 inhibits PP2A activity to regulate IRE-1/XBP-1 signaling. Cardiac-specific Pak2 deletion impairs UPR, causes cardiac dysfunction, and increased cell death under ER stress or pressure overload. Cardiac-specific Pak2 conditional KO mice, tunicamycin and pressure overload models, gene array, PP2A activity assay, IRE-1/XBP-1 pathway analysis, AAV9-XBP1s rescue, chemical chaperone treatment Circulation research High 30620686
2019 PAK2 promotes cellular senescence by regulating HIRA-mediated deposition of histone H3.3 onto chromatin and expression of senescence genes. PAK2 depletion delays oncogene-induced and oxidative stress-induced senescence, while overexpression accelerates it. In BubR1 progeroid mice, Pak2 depletion attenuates aging phenotypes and extends lifespan. PAK2 siRNA depletion and overexpression in human fibroblasts, MEF oxidative stress model, H3.3 chromatin deposition assay, senescence gene expression, BubR1 progeroid mouse model Proceedings of the National Academy of Sciences of the United States of America High 31209047
2014 Rac1 (but not Cdc42 or RhoA) recruits PAK2 to G2 phase centrosomes in a cell cycle-dependent manner. PAK2 activation at centrosomes is required for activation of Aurora A and the CyclinB/Cdk1 complex, and Rac1 inhibition delays mitotic entry. Centrosome preparation by sucrose gradient, immunofluorescence, Rac1 inhibition by C. difficile toxin B glucosylation or knockout, Aurora A and Cdk1 activation assays Cell cycle Medium 24840740
2018 CDK12 directly binds to and phosphorylates PAK2 at T134 and T169, activating MAPK signaling in gastric cancer. CDK12 inhibition with procaterol reduces PAK2 activation and tumor growth. Co-IP, mass spectrometry, computer docking, in vitro kinase assay, RNAi, cell xenograft and PDX mouse models Theranostics Medium 32483448
2018 PKM2 directly phosphorylates PAK2 at Ser-20, Ser-141, and Ser-192/197 in vitro. Phosphorylation at Ser-192/197 promotes PAK2-HSP90 association, stabilizing PAK2 protein by reducing ubiquitin-dependent proteasomal degradation. PKM2 knockdown decreases PAK2 protein half-life. In vitro binding and kinase assay, site mutagenesis, co-IP (PAK2-HSP90), ubiquitin proteasomal degradation assay, xenograft metastasis model Oncogene High 29335522
2011 Full-length PAK2 knockout results in early embryonic lethality, while mice expressing a caspase cleavage-deficient PAK2 (D212N) are viable, demonstrating that full-length PAK2 is essential for embryonic development but caspase-activated PAK2p34 generation is not required for viability. Caspase-cleaved PAK2p34 amplifies the apoptotic response via positive feedback through effector caspases 3, 6, and 7. PAK2 knockout mice, PAK2D212N knock-in mice, MEF spontaneous and cisplatin-induced cell death, effector caspase activity assays Mammalian genome High 21499899
2020 Cdc42-activated full-length PAK2 is resistant to caspase-3 cleavage in vitro and in cells. Under mild stress (serum deprivation) or Cdc42 activation, PAK2 becomes refractory to caspase-3-mediated apoptotic activation, thereby inhibiting apoptosis. This identifies two mutually exclusive PAK2 activation states that function as a molecular switch between cytostasis and apoptosis. In vitro caspase-3 cleavage assay with Cdc42-activated vs. full-length PAK2, H2O2-induced apoptosis, PAK2 active-mutant expression, cell death assays Biochimica et biophysica acta. Molecular cell research High 31926209
2019 E-cadherin recruits and activates PAK2 in response to mechanical force, enabling cells to stiffen and survive. PAK2 activation is force amplitude-dependent: at low force amplitudes, AMPK directly binds and protects PAK2 from proteolysis (ensuring cell survival); at high force amplitudes, PAK2 is cleaved and promotes apoptosis. Cleavage-resistant PAK2 forms prevent force-induced apoptosis. Force application to E-cadherin, PAK2 activation assay, AMPK co-immunoprecipitation/binding assay, PAK2 cleavage assay, cleavage-resistant PAK2 mutant, cell stiffness measurement, metabolic assays The Journal of cell biology High 30940647
2004 PS-GAP (a GTPase-activating protein for Cdc42/RhoA) interacts specifically with caspase-activated PAK-2p34 but not with active or inactive full-length PAK-2. PS-GAP binding inhibits PAK-2p34 kinase activity and changes its localization from the nucleus to the perinuclear region, reducing cell death stimulated by PAK-2p34. Co-immunoprecipitation, kinase activity assay, immunofluorescence localization, cell death assay The Journal of biological chemistry Medium 15471851
2016 PAK2 (but not PAK1) is required for Pak2-dependent paxillin phosphorylation and focal adhesion remodeling in response to angiopoietin-1 (Ang-1)/Tie2 signaling in endothelial cells. PAK2 and paxillin are required for Ang-1-induced Cdc42 activation at leading edges, Par3 recruitment, and formation of a Par3-PAK2-paxillin polarity complex at focal adhesions to drive EC polarization and angiogenic sprouting. siRNA knockdown of PAK2 and paxillin, Cdc42 activation assay, co-immunoprecipitation, immunofluorescence, EC polarization and sprouting assays Molecular biology of the cell Medium 31141452
2023 PAK2 recruits septin hetero-oligomers to form a ring around exocytic sites in endothelial cells. This PAK2-septin cascade controls actomyosin ring function for efficient exocytic release of von Willebrand factor (VWF). Genetic or pharmacological PAK2 inhibition leads to inefficient VWF release and failure to form platelet-catching strings. APEX2 proximity labeling, dual loss-of-function screen, co-immunoprecipitation, genetic PAK2 inhibition, pharmacological PAK2 inhibition, VWF release assay, platelet string formation assay Blood High 36564030
2022 PAK2 mediates Hrd1 E3 ubiquitin ligase expression, which targets Nrf2 for ubiquitination and degradation in the stressed heart, preventing aberrant Nrf2 activation. PAK2 also enhances the XBP1-Hrd1 UPR axis. In the absence of Pak2, Nrf2 accumulates and switches from antioxidant roles to activating RAAS genes, worsening heart failure. Pak2 cardiac KO, AAV9-Pak2 delivery, Nrf2 ubiquitination assay, Hrd1 expression assay, XBP1-Hrd1 axis analysis, iPSC-CM model, human dilated cardiomyopathy samples Frontiers in cardiovascular medicine Medium 35350536

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science (New York, N.Y.) 601 9171063
1995 A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. The EMBO journal 327 7744004
2008 Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling. Journal of cell science 164 18319301
1996 Rac "insert region" is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. The Journal of biological chemistry 133 8702687
2000 Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2. The Journal of biological chemistry 124 10748018
2003 Cell-type-specific activation of PAK2 by transforming growth factor beta independent of Smad2 and Smad3. Molecular and cellular biology 116 14612425
2002 Phosphorylation of p85 beta PIX, a Rac/Cdc42-specific guanine nucleotide exchange factor, via the Ras/ERK/PAK2 pathway is required for basic fibroblast growth factor-induced neurite outgrowth. The Journal of biological chemistry 112 12226077
2008 Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms. Molecular and cellular biology 108 18411304
2000 Endothelial cell retraction is induced by PAK2 monophosphorylation of myosin II. Journal of cell science 104 10639334
2008 Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2. EMBO reports 88 18344974
2011 Proteome analysis of erythrocytes lacking AMP-activated protein kinase reveals a role of PAK2 kinase in eryptosis. Journal of proteome research 84 21214270
2018 PAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior. Cell reports 79 30134165
2006 Posttranslational myristoylation of caspase-activated p21-activated protein kinase 2 (PAK2) potentiates late apoptotic events. Proceedings of the National Academy of Sciences of the United States of America 77 16617111
2018 PAK2-c-Myc-PKM2 axis plays an essential role in head and neck oncogenesis via regulating Warburg effect. Cell death & disease 74 30068946
2019 Long non-coding RNA ZEB1-AS1 promotes colon adenocarcinoma malignant progression via miR-455-3p/PAK2 axis. Cell proliferation 70 31828845
2019 Pak2 as a Novel Therapeutic Target for Cardioprotective Endoplasmic Reticulum Stress Response. Circulation research 69 30620686
2004 Negative control of the Myc protein by the stress-responsive kinase Pak2. Molecular and cellular biology 69 14749374
2000 Lentivirus Nef specifically activates Pak2. Journal of virology 67 11070003
2009 Identification of MYO18A as a novel interacting partner of the PAK2/betaPIX/GIT1 complex and its potential function in modulating epithelial cell migration. Molecular biology of the cell 66 19923322
2003 Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation. The Journal of biological chemistry 66 12853446
2006 Transforming growth factor beta activation of c-Abl is independent of receptor internalization and regulated by phosphatidylinositol 3-kinase and PAK2 in mesenchymal cultures. The Journal of biological chemistry 63 16867995
2019 ROCK1 but not LIMK1 or PAK2 is a key regulator of apoptotic membrane blebbing and cell disassembly. Cell death and differentiation 61 31043701
2018 Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and metastasis through phosphorylation and stabilization of PAK2 protein. Oncogene 59 29335522
2020 CDK12 and PAK2 as novel therapeutic targets for human gastric cancer. Theranostics 56 32483448
2001 Human immunodeficiency virus type 1 Nef selectively associates with a catalytically active subpopulation of p21-activated kinase 2 (PAK2) independently of PAK2 binding to Nck or beta-PIX. Journal of virology 55 11160719
2005 Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2. The EMBO journal 54 16281055
2010 Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling. Journal of virology 52 20147394
2016 Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells. Oncotarget 51 26919098
1998 Caspase-mediated activation of PAK2 during apoptosis: proteolytic kinase activation as a general mechanism of apoptotic signal transduction? Cell death and differentiation 50 10200518
2014 Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation. eLife 49 24843022
1999 PAK2 is cleaved and activated during hyperosmotic shock-induced apoptosis via a caspase-dependent mechanism: evidence for the involvement of oxidative stress. Journal of cellular physiology 49 9989786
2015 Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization. Blood 47 25824689
2020 Meteorin-Like (METRNL) Attenuates Myocardial Ischemia/Reperfusion Injury-Induced Cardiomyocytes Apoptosis by Alleviating Endoplasmic Reticulum Stress via Activation of AMPK-PAK2 Signaling in H9C2 Cells. Medical science monitor : international medical journal of experimental and clinical research 46 32594095
2019 MicroRNA-455-3p promotes TGF-β signaling and inhibits osteoarthritis development by directly targeting PAK2. Experimental & molecular medicine 46 31586040
2019 MicroRNA-7-5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non-small cell lung cancer. FEBS open bio 45 31587474
2012 Altered nitric oxide production mediates matrix-specific PAK2 and NF-κB activation by flow. Molecular biology of the cell 43 23171552
2006 Crystal structure of the SH3 domain of betaPIX in complex with a high affinity peptide from PAK2. Journal of molecular biology 43 16527308
2002 Cdc42/Rac1-mediated activation primes PAK2 for superactivation by tyrosine phosphorylation. Molecular and cellular biology 42 12215529
2018 MicroRNA miR-4779 suppresses tumor growth by inducing apoptosis and cell cycle arrest through direct targeting of PAK2 and CCND3. Cell death & disease 41 29362401
2009 Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta. Developmental cell 41 19289088
1998 Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells. Journal of cellular biochemistry 40 9712143
2015 miR-137 inhibits proliferation of melanoma cells by targeting PAK2. Experimental dermatology 39 26186482
2015 PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex. Scientific reports 39 26412398
2000 Regulation of Xenopus p21-activated kinase (X-PAK2) by Cdc42 and maturation-promoting factor controls Xenopus oocyte maturation. The Journal of biological chemistry 37 10644687
2009 PAK1 and PAK2 have different roles in HGF-induced morphological responses. Cellular signalling 35 19628037
2018 IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer. Oncogene 34 29353882
2010 P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation. Carcinogenesis 34 21177766
2004 Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. The Journal of biological chemistry 34 15234964
2016 Dual Site Phosphorylation of Caspase-7 by PAK2 Blocks Apoptotic Activity by Two Distinct Mechanisms. Structure (London, England : 1993) 33 27889207
2019 Pak2 kinase promotes cellular senescence and organismal aging. Proceedings of the National Academy of Sciences of the United States of America 31 31209047
2016 The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events. Biochimica et biophysica acta 31 26912410
2016 P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells. Molecular and cellular endocrinology 31 27040307
2009 Huntingtin promotes cell survival by preventing Pak2 cleavage. Journal of cell science 31 19240112
2005 Regulation of the interaction of Pak2 with Cdc42 via autophosphorylation of serine 141. The Journal of biological chemistry 31 16204230
2004 Activation of Syk protein tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2/gamma-PAK. Molecular and cellular biology 31 14673144
2024 Molecular mechanisms of pancreatic cancer liver metastasis: the role of PAK2. Frontiers in immunology 30 38343537
2020 LINC00858 promotes colorectal cancer by sponging miR-4766-5p to regulate PAK2. Cell biology and toxicology 30 31902050
2009 Activation of JNK and PAK2 is essential for citrinin-induced apoptosis in a human osteoblast cell line. Environmental toxicology 29 18767140
2003 Localization of p21-activated protein kinase gamma-PAK/Pak2 in the endoplasmic reticulum is required for induction of cytostasis. The Journal of biological chemistry 29 12560339
2015 Association with PAK2 Enables Functional Interactions of Lentiviral Nef Proteins with the Exocyst Complex. mBio 28 26350970
2012 Pak2 kinase restrains mast cell FcεRI receptor signaling through modulation of Rho protein guanine nucleotide exchange factor (GEF) activity. The Journal of biological chemistry 28 23204526
2011 Mutation screening of the 3q29 microdeletion syndrome candidate genes DLG1 and PAK2 in schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 28 21850710
2008 Analysis of conformational changes during activation of protein kinase Pak2 by amide hydrogen/deuterium exchange. The Journal of biological chemistry 28 18984590
1998 Heat shock stress induces cleavage and activation of PAK2 in apoptotic cells. Journal of protein chemistry 28 9717744
2014 Rac1-dependent recruitment of PAK2 to G2 phase centrosomes and their roles in the regulation of mitotic entry. Cell cycle (Georgetown, Tex.) 26 24840740
2012 p21-Activated kinase 2 (PAK2) inhibits TGF-β signaling in Madin-Darby canine kidney (MDCK) epithelial cells by interfering with the receptor-Smad interaction. The Journal of biological chemistry 26 22393057
2012 A βPIX-PAK2 complex confers protection against Scrib-dependent and cadherin-mediated apoptosis. Current biology : CB 26 22863318
2003 Evaluation of the catalytic mechanism of the p21-activated protein kinase PAK2. Biochemistry 26 12549935
2019 MiR-216a-5p act as a tumor suppressor, regulating the cell proliferation and metastasis by targeting PAK2 in breast cancer. European review for medical and pharmacological sciences 25 30964173
2019 Melatonin ameliorates endoplasmic reticulum stress in N2a neuroblastoma cell hypoxia-reoxygenation injury by activating the AMPK-Pak2 pathway. Cell stress & chaperones 25 30976981
2023 Recurrent PAK2 rearrangements in poroma with folliculo-sebaceous differentiation. Histopathology 24 37199682
2022 Pak2 Regulation of Nrf2 Serves as a Novel Signaling Nexus Linking ER Stress Response and Oxidative Stress in the Heart. Frontiers in cardiovascular medicine 24 35350536
2020 PAK2 activated by Cdc42 and caspase 3 mediates different cellular responses to oxidative stress-induced apoptosis. Biochimica et biophysica acta. Molecular cell research 24 31926209
2014 Motility of select ovarian cancer cell lines: effect of extra-cellular matrix proteins and the involvement of PAK2. International journal of oncology 24 25050916
2015 Pak2 regulates hematopoietic progenitor cell proliferation, survival, and differentiation. Stem cells (Dayton, Ohio) 23 25586960
2019 PAK2 links cell survival to mechanotransduction and metabolism. The Journal of cell biology 22 30940647
2019 Melatonin-Mediated Pak2 Activation Reduces Cardiomyocyte Death Through Suppressing Hypoxia Reoxygenation Injury-Induced Endoplasmic Reticulum Stress. Journal of cardiovascular pharmacology 22 31274839
2012 Paracrine signalling in colorectal liver metastases involving tumor cell-derived PDGF-C and hepatic stellate cell-derived PAK-2. Clinical & experimental metastasis 22 22362252
2022 Cancer-released exosomal circular RNA circ_0008717 promotes cell tumorigenicity through microRNA-1287-5p/P21-activated kinase 2 (PAK2) axis in non-small cell lung cancer. Bioengineered 21 35333693
2020 Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle. The Journal of physiology 21 32844438
2018 miR-26a inhibits proliferation and promotes apoptosis in porcine immature Sertoli cells by targeting the PAK2 gene. Reproduction in domestic animals = Zuchthygiene 21 30024056
2004 Identification and characterization of PS-GAP as a novel regulator of caspase-activated PAK-2. The Journal of biological chemistry 21 15471851
2025 Discovery of PAK2 as a Key Regulator of Cancer Stem Cell in Head and Neck Squamous Cell Carcinoma Using Multi-Omic Techniques. Stem cells international 20 41311809
2022 LncRNA FAF attenuates hypoxia/ischaemia-induced pyroptosis via the miR-185-5p/PAK2 axis in cardiomyocytes. Journal of cellular and molecular medicine 20 35373434
2019 Polarization and sprouting of endothelial cells by angiopoietin-1 require PAK2 and paxillin-dependent Cdc42 activation. Molecular biology of the cell 20 31141452
2023 Proximity proteomics identifies septins and PAK2 as decisive regulators of actomyosin-mediated expulsion of von Willebrand factor. Blood 19 36564030
2020 Pak2 inhibition promotes resveratrol-mediated glioblastoma A172 cell apoptosis via modulating the AMPK-YAP signaling pathway. Journal of cellular physiology 19 32017068
2019 PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions. Scientific reports 19 31748572
2014 Prostasin may contribute to chemoresistance, repress cancer cells in ovarian cancer, and is involved in the signaling pathways of CASP/PAK2-p34/actin. Cell death & disease 19 24434518
2010 Pak1 and Pak2 are activated in recurrent respiratory papillomas, contributing to one pathway of Rac1-mediated COX-2 expression. International journal of cancer 19 20131316
2021 miR-107 regulates the effect of MCM7 on the proliferation and apoptosis of colorectal cancer via the PAK2 pathway. Biochemical pharmacology 18 34010598
2021 PAK1 and PAK2 in cell metabolism regulation. Journal of cellular biochemistry 18 34750857
2016 PAK2 promotes migration and proliferation of salivary gland adenoid cystic carcinoma. American journal of translational research 18 27648129
2011 Functional PAK-2 knockout and replacement with a caspase cleavage-deficient mutant in mice reveals differential requirements of full-length PAK-2 and caspase-activated PAK-2p34. Mammalian genome : official journal of the International Mammalian Genome Society 18 21499899
2021 hsa_circ_0013401 Accelerates the Growth and Metastasis and Prevents Apoptosis and Autophagy of Neuroblastoma Cells by Sponging miR-195 to Release PAK2. Oxidative medicine and cellular longevity 17 34853631
2017 Pak2 regulates myeloid-derived suppressor cell development in mice. Blood advances 17 29296839
2024 ACSL4 promotes malignant progression of Hepatocellular carcinoma by targeting PAK2 transcription. Biochemical pharmacology 16 38615921
2023 Circular RNA 0001789 sponges miR-140-3p and regulates PAK2 to promote the progression of gastric cancer. Journal of translational medicine 15 36740679
2016 Rac1-PAK2 pathway is essential for zebrafish heart regeneration. Biochemical and biophysical research communications 15 26966072
2007 Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK. Biochemistry 15 18161990

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