Affinage

PAK1

Serine/threonine-protein kinase PAK 1 · UniProt Q13153

Length
545 aa
Mass
60.6 kDa
Annotated
2026-04-29
100 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAK1 is a Rac1/Cdc42-activated serine/threonine kinase that serves as a central integrator of cytoskeletal dynamics, MAPK signaling, and diverse tissue-specific physiological processes. Upon release from its autoinhibitory homodimer—whose crystal structure reveals an intermediate-active kinase domain conformation even without Thr423 phosphorylation—PAK1 phosphorylates LIM-kinase (Thr508), myosin light chain, cortactin, Raf-1 (Ser338), ATG5 (Thr101), SHARP, and paxillin to control actin remodeling, directed cell migration, invadopodia turnover, ERK cascade activation (including a kinase-independent scaffold function bridging Rac1 to MEK1), Notch target gene repression, and autophagosome formation (PMID:10559936, PMID:10330410, PMID:11733498, PMID:24859002, PMID:32186433, PMID:15824732, PMID:23653349). Beyond cytoskeletal regulation, PAK1 is essential for insulin-stimulated GLUT4 translocation in skeletal muscle, SERCA2a-dependent cardiac Ca²⁺ homeostasis, oligodendrocyte myelination, nuclear mechanotransduction in fibroblasts, and NFAT activation downstream of the T-cell receptor (PMID:35222279, PMID:25217043, PMID:33478987, PMID:37967011, PMID:9755165). De novo gain-of-function PAK1 mutations (Y131C, Y429C) that impair autoinhibitory dimerization cause a neurodevelopmental disorder with enhanced JNK/AKT signaling (PMID:30290153).

Mechanistic history

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

    Establishing PAK1 as a kinase effector downstream of Rac/Cdc42 GTPases that activates stress-activated MAP kinase pathways answered the fundamental question of how Rho-family GTPase signals reach p38 and JNK cascades.

    Evidence Dominant-negative PAK1 blocks Rac/Cdc42- and IL-1-induced p38 activation in co-expression assays

    PMID:7592586

    Open questions at the time
    • Direct phosphorylation of MAP3K intermediates not shown
    • Upstream mechanism of PAK1 activation not yet defined
  2. 1996 High

    Identification of the Nck adapter as a direct PAK1-binding partner via SH3-domain interactions revealed how receptor tyrosine kinase signaling (e.g., PDGFR) recruits PAK1 to signaling complexes.

    Evidence Reciprocal co-IP and in vitro binding with domain mapping of Nck SH3-2 and PAK1 proline-rich motif

    PMID:8824201

    Open questions at the time
    • Functional consequence of Nck-mediated PAK1 recruitment not yet demonstrated
  3. 1997 High

    Demonstrating that activated PAK1 directly reorganizes the actin cytoskeleton—inducing filopodia and membrane ruffles—and localizes to F-actin-rich structures established PAK1 as a direct cytoskeletal effector rather than merely a kinase cascade component.

    Evidence Microinjection of activated PAK1, immunofluorescence co-localization with F-actin, co-IP with filamentous actin, pharmacological inhibitor studies

    PMID:9298982 PMID:9395435

    Open questions at the time
    • Direct actin-binding substrates not yet identified
    • Kinase-dependent vs. kinase-independent cytoskeletal effects not resolved
  4. 1998 High

    Placing PAK1 in TCR signaling downstream of Lck/Vav/Cdc42 and upstream of NFAT and ERK2 (but not JNK) demonstrated PAK1 functions in immune cell gene expression beyond stress kinase cascades.

    Evidence Dominant-negative PAK1 blocks NFAT and ERK2 reporters in T cells; co-IP with phospho-Nck after TCR stimulation

    PMID:9755165

    Open questions at the time
    • Direct substrates mediating NFAT activation not identified
  5. 1999 High

    Identification of LIM-kinase Thr508 and myosin light chain as direct PAK1 substrates connected PAK1 activity to specific molecular steps in actin depolymerization and directed cell motility.

    Evidence In vitro kinase assay with mutagenesis for LIMK Thr508; inducible expression of kinase-dead/active PAK1 with MLC phosphorylation and chemotaxis readouts

    PMID:10330410 PMID:10559936

    Open questions at the time
    • Whether PAK1 phosphorylates MLC directly or through MLCK not fully resolved
    • Spatial regulation of substrate phosphorylation in vivo unclear
  6. 2001 High

    Discovery that PAK1 directly phosphorylates Raf-1 at Ser338 established PAK1 as a critical input for MAPK/ERK cascade activation independent of Ras-mediated Raf recruitment.

    Evidence Co-IP of endogenous PAK1–Raf-1 complex, in vitro kinase assay showing Ser338 phosphorylation, domain mapping

    PMID:11733498

    Open questions at the time
    • Relative contribution of PAK1 vs. other Raf-1 Ser338 kinases in vivo unknown
  7. 2002 High

    Showing that PI3K binds and activates PAK1 independently of Cdc42/Rac1 revealed a second, GTPase-independent activation route and direct actin phosphorylation as a mechanism for stress fiber dissolution.

    Evidence Co-IP with domain mapping, in vitro kinase assay on actin, kinase-dead control

    PMID:12181358

    Open questions at the time
    • Physiological relevance of direct actin phosphorylation needs in vivo confirmation
    • Actin phosphorylation site not mapped
  8. 2003 High

    Multiple discoveries expanded PAK1's interaction network: cardiac localization with PP2A and troponin I regulation, EGFR-Grb2-mediated recruitment to membranes, and Cdk5-mediated Thr212 phosphorylation in neurons broadened PAK1 function to cardiac contractility and neuronal development.

    Evidence Co-IP in cardiac myocytes with Ca²⁺-tension measurements; Grb2 binding via SH3 domain with TAT-peptide competition; phospho-specific antibody in embryonic brain

    PMID:12522133 PMID:12950086 PMID:14670848

    Open questions at the time
    • Direct troponin I phosphatase mechanism downstream of PAK1-PP2A unclear
    • Functional consequence of Thr212 phosphorylation in neurons not shown
  9. 2004 High

    Demonstration that ERK2 phosphorylates PAK1 at Thr212 in an adhesion-dependent manner, with the phosphomimetic attenuating ERK signaling, established a negative feedback loop between PAK1 and the ERK pathway.

    Evidence Far-western confirming direct interaction, in vitro kinase assay with site mapping, phosphomimetic reporter assay

    PMID:15542607

    Open questions at the time
    • In vivo significance of feedback loop not tested genetically
  10. 2005 High

    Crystal structures at 1.8 Å resolution revealing that the PAK1 kinase domain adopts a near-active conformation even without Thr423 phosphorylation fundamentally reframed the activation model: autoinhibitory dimerization, not activation-loop phosphorylation, is the primary constraint on activity.

    Evidence X-ray crystallography of free and phosphomimetic kinase domains

    PMID:15893667

    Open questions at the time
    • Full-length PAK1 dimer structure not solved
    • Dynamics of dimer-to-monomer transition not captured
  11. 2005 High

    Identification of CIB1 as a calcium-dependent PAK1 activator and CRIPak as an endogenous PAK1 inhibitor defined two new regulatory inputs controlling PAK1 kinase output and its downstream effects on LIMK/cofilin.

    Evidence In vitro kinase activation by CIB1, siRNA depletion reducing adhesion-induced PAK1 activation; CRIPak Co-IP and in vitro kinase inhibition with siRNA derepression

    PMID:16061695 PMID:16278681

    Open questions at the time
    • CIB1 and CRIPak binding sites on PAK1 not precisely mapped structurally
    • In vivo physiological contexts for CIB1/CRIPak regulation not established
  12. 2007 High

    Demonstration that Chp GTPase triggers PAK1 autophosphorylation-dependent ubiquitination and proteasomal degradation revealed a turnover mechanism distinct from kinase activation, explaining how cells reset PAK1 signaling.

    Evidence Ubiquitination assay with proteasome inhibitor, domain mapping with kinase-dead and autophosphorylation-site mutants

    PMID:17355222

    Open questions at the time
    • E3 ubiquitin ligase identity not determined
    • Physiological trigger for Chp-mediated PAK1 degradation unclear
  13. 2009 High

    A FRET-based conformational biosensor revealed that PAK1 adopts an intermediate semi-open state at the plasma membrane, selectively autophosphorylated on N-terminal serines, providing the first real-time visualization of spatially regulated PAK1 activation dynamics.

    Evidence FRET biosensor in live cells with pharmacological and genetic perturbations

    PMID:19574218

    Open questions at the time
    • Structural basis of semi-open intermediate not resolved
    • Whether intermediate state exists for other PAK family members unknown
  14. 2011 High

    PAK1 knockout mice revealed essential roles in glucose homeostasis: PAK1 is required for sustained insulin secretion from β-cells and for GLUT4 translocation in skeletal muscle via cofilin phosphorylation, linking cytoskeletal kinase function to metabolic regulation.

    Evidence Global PAK1 KO with glucose tolerance testing, islet insulin secretion, GLUT4 translocation, and ERK/cofilin phosphorylation readouts

    PMID:21969371

    Open questions at the time
    • Tissue-specific contributions not dissected in this global KO
    • Direct PAK1 substrates in β-cell exocytosis not identified
  15. 2013 Medium

    Discovery that kinase-dead PAK1 still promotes MEK/ERK activation by scaffolding a Rac1–PAK1–MEK1 complex established a kinase-independent mechanism for MAPK pathway engagement, broadening PAK1's signaling repertoire beyond its catalytic activity.

    Evidence Kinase-dead PAK1 overexpression increases MEK/ERK phosphorylation; co-IP of Rac1-PAK1-MEK1 triple complex

    PMID:23653349

    Open questions at the time
    • Scaffold function not yet shown with endogenous protein levels
    • Structural basis of scaffold interaction unknown
    • Single-lab finding
  16. 2014 High

    Multiple studies defined PAK1 as an effector in invadopodia dynamics (phosphorylating cortactin downstream of Trio-Rac1), cardiac physiology (regulating SERCA2a via SRF transcription in cardiomyocytes), and as a paxillin Ser258 kinase in HIV Nef-mediated vesicle trafficking.

    Evidence FRET/photoactivation for invadopodia; conditional cardiac KO with Ca²⁺ imaging and SERCA2a qPCR; site-specific phospho-mapping of paxillin with mutagenesis

    PMID:23317503 PMID:24859002 PMID:25217043

    Open questions at the time
    • How PAK1-cortactin phosphorylation triggers disassembly structurally undefined
    • SRF cofactor mediating PAK1 transcriptional effect not identified
  17. 2018 High

    Patient mutations (Y131C, Y429C) that reduce PAK1 dimerization cause constitutive kinase activation, linking the autoinhibitory dimer model to human neurodevelopmental disease and validating dimerization as the primary restraint on PAK1 activity in vivo.

    Evidence Co-IP and SEC showing reduced dimerization, enhanced JNK/AKT phosphorylation in patient fibroblasts, rescue by PAK1 inhibitor FRAX486

    PMID:30290153

    Open questions at the time
    • Full spectrum of downstream targets dysregulated by gain-of-function mutations not catalogued
    • Neuronal-specific pathomechanism not dissected
  18. 2020 High

    Identification of ELP3-mediated acetylation at K420 as an activation switch that drives PAK1-dependent ATG5 Thr101 phosphorylation and autophagosome formation connected PAK1 to autophagy regulation via a hypoxia-responsive post-translational code.

    Evidence In vitro kinase assay, K420 acetylation/deacetylation mutagenesis, ubiquitination assay for ATG5, autophagy flux measurement

    PMID:32186433

    Open questions at the time
    • In vivo relevance of ELP3-PAK1-ATG5 axis in tissue-specific autophagy not tested
    • Whether SIRT1-mediated deacetylation is the sole eraser unknown
  19. 2021 High

    Identification of the Smad4-MYO18A-PP1A complex as the phosphatase targeting PAK1-Thr423 resolved how PAK1 activity is terminated and connected PAK1 inactivation to suppression of β-catenin nuclear translocation.

    Evidence LC-MS/MS identification, in vitro phosphatase assay, domain mapping of RVFFR motif, β-catenin localization in cholangiocarcinoma cells

    PMID:34799729

    Open questions at the time
    • Whether this phosphatase complex operates in tissues beyond cholangiocarcinoma not tested
    • Other PAK1 phosphatases may exist
  20. 2022 High

    Inducible skeletal-muscle-specific PAK1 knockout confirmed a non-redundant role in GLUT4 translocation via ARPC1B and revealed muscle-to-β-cell crosstalk through secreted factors, establishing PAK1 as a systemic metabolic regulator.

    Evidence Inducible muscle-specific KO/OE mice, glucose/insulin tolerance, GLUT4-myc translocation, conditioned media on β-cells

    PMID:35222279

    Open questions at the time
    • Identity of PAK1-dependent myokines unknown
    • ARPC1B phosphorylation site not mapped
  21. 2023 Medium

    Demonstration that PAK1 drives nuclear softening and H3K9Me3 heterochromatin loss in mechanically stressed fibroblasts, with PAK1 loss improving fibrosis in vivo, revealed a nuclear mechanotransduction function beyond its classical cytoplasmic roles.

    Evidence Genetic PAK1 manipulation with ATAC-seq, RNA-seq, nuclear mechanics, mouse liver/lung fibrosis models

    PMID:37967011

    Open questions at the time
    • Direct nuclear substrates of PAK1 mediating chromatin remodeling not identified
    • Whether PAK1 translocates to the nucleus or acts through cytoplasmic intermediaries unclear
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length autoinhibitory dimer structure, the identity of the E3 ligase(s) mediating PAK1 ubiquitination, the direct nuclear substrates through which PAK1 remodels chromatin, and the identity of PAK1-dependent myokines mediating muscle-to-islet crosstalk.
  • Full-length PAK1 dimer crystal structure not available
  • E3 ubiquitin ligase for Chp-induced PAK1 degradation unknown
  • Nuclear mechanotransduction substrates not identified
  • Myokine identity downstream of muscle PAK1 undefined

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 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 2 R-HSA-382551 Transport of small molecules 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
ARHGEF7CDC42CIB1GRB2LIMK1NCK1RAC1RAF1
Complex memberships
PAK1 autoinhibitory homodimer

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PAK1 directly phosphorylates LIM-kinase at threonine 508 within its activation loop, increasing LIM-kinase-mediated phosphorylation of cofilin tenfold in vitro; activated Rac/Cdc42 increases PAK1-LIMK association requiring both N-terminal regulatory and C-terminal catalytic domains of PAK1, thereby coupling Rac/Cdc42 signaling to actin depolymerization In vitro kinase assay, co-immunoprecipitation, dominant-negative interference, PAK1 autoinhibitory domain peptide inhibitor Nature cell biology High 10559936
1995 PAK1 acts as a downstream mediator of Rac/Cdc42 GTPases to activate the p38 MAP kinase; dominant-negative PAK1 suppresses both IL-1- and Rac/Cdc42-induced p38 activity, placing PAK1 in a kinase cascade leading to p38 and JNK activation Co-expression of constitutively active/dominant-negative GTPases and PAK1, p38 kinase activity assay The Journal of biological chemistry High 7592586
1997 PAK1 regulates actin cytoskeletal organization in mammalian cells; microinjection of activated PAK1 induces filopodia and membrane ruffles; PAK1 N-terminal mutants that cannot bind Cdc42/Rac1 show enhanced binding to the adapter protein Nck via a proline-rich SH3-binding region, and mutation of this proline residue alters cytoskeletal effects Microinjection, overexpression of mutants, co-immunoprecipitation, fluorescence microscopy Current biology High 9395435
1996 PAK1 specifically interacts with the Nck adapter protein both in vitro and in vivo; Nck binds PAK1 through its second SH3 domain while PAK1 interacts with Nck via its first proline-rich SH3-binding motif; active PAK1 phosphorylates Nck at multiple sites; this interaction is strengthened upon PDGF receptor stimulation Co-immunoprecipitation, in vitro binding assay, in vivo phosphorylation assay The Journal of biological chemistry High 8824201
1997 Endogenous PAK1 localizes to pinocytic vesicles and co-localizes with F-actin in membrane ruffles and lamellipodia upon PDGF stimulation or Rac1 activation; PAK1 precedes F-actin in translocating to peripheral cytoskeletal structures; co-immunoprecipitation demonstrates in vivo interaction of PAK1 with filamentous actin; localization to actin structures is blocked by cytochalasin D and wortmannin Immunofluorescence microscopy, subcellular fractionation, co-immunoprecipitation, microinjection, pharmacological inhibition The Journal of cell biology High 9298982
1999 Constitutively active PAK1 increases myosin light chain (MLC) phosphorylation and promotes directional cell motility; kinase-dead PAK1 has no effect on MLC phosphorylation and causes defects in directed motility; PAK1 kinase activity is required for polarized lamellipodia formation and persistent directional movement on fibronectin Tetracycline-inducible expression of wild-type, kinase-dead, and constitutively active PAK1; F-actin staining; MLC phosphorylation western blot; motility and chemotaxis assays The Journal of cell biology High 10330410
2000 Activated (phosphorylated) PAK1 localizes to focal adhesions, filopodia, and lamellipodia edges in response to Cdc42/Rac1 or PDGF stimulation; PAK1 activation during wound closure is rapid, localizes to the leading edge, and is blocked by PI3-kinase and Src family kinase inhibitors but not EGFR inhibitor Phospho-specific antibody immunofluorescence, pharmacological inhibition, wound-healing assay The Journal of cell biology High 11134074
2001 PAK1 directly associates with Raf-1 in a manner dependent on PAK1's active conformation; active PAK1 phosphorylates Raf-1 at Ser338, a critical step for Raf-1 activation; the Raf-1 binding site maps to the C-terminus of the PAK1 catalytic domain; kinase-dead PAK1 barely binds Raf-1 Co-immunoprecipitation under physiological and overexpressed conditions, in vitro kinase assay, domain mapping with deletion mutants, active-site mutagenesis The Journal of biological chemistry High 11733498
2002 PI-3 kinase associates with the N-terminal regulatory domain (amino acids 67-150) of PAK1 in a Cdc42/Rac1-independent manner, leading to PAK1 activation; activated PAK1 directly phosphorylates actin, resulting in stress fiber dissolution and microfilament redistribution; kinase-dead PAK1 (K299R) and autoinhibitory domain peptide block actin phosphorylation Co-immunoprecipitation, in vitro kinase assay, domain mapping with deletion/point mutants, cytoskeletal imaging Molecular biology of the cell High 12181358
2003 PAK1 physically interacts with protein phosphatase 2A (PP2A) and localizes to Z-disk, cell membrane, intercalated disc, and nuclear membrane in rat cardiac myocytes; constitutively active PAK1 reduces phosphorylation of cardiac troponin I (cTnI) and myosin binding protein C, associated with increased Ca2+ sensitivity Co-immunoprecipitation, adenoviral overexpression, immunofluorescence, Ca2+-tension measurements Circulation research High 14670848
2003 PAK1 interacts with the Grb2 adapter protein via its second proline-rich SH3-binding domain; Grb2 mediates PAK1 association with the activated EGFR; blockade of this interaction by a cell-permeant TAT-tagged peptide decreased EGF-induced membrane lamellar extension Co-immunoprecipitation, in vitro binding, TAT-peptide competition assay, cell morphology analysis The Journal of biological chemistry High 12522133
2003 PAK1 Thr212 is phosphorylated by Cdk5 (p35/Cdk5) or cyclin B1/Cdc2 in postmitotic neurons and mitotic cells respectively; developmental analysis shows Pak1T212(PO4) accumulates in corpus callosum, intermediate zone, and olfactory/commissural tracts in embryonic forebrain, and is absent in adult tissues Phospho-specific antibody immunofluorescence, developmental expression analysis, site-specific biochemical characterization Developmental dynamics Medium 12950086
2005 Crystal structures of the free PAK1 kinase domain at 1.8 Å resolution reveal an essentially active conformation even without phosphorylation of Thr423; a phosphomimetic activation-loop mutation yields a very similar active conformation; the unphosphorylated kinase domain adopts an 'intermediate-active' state upon release from autoinhibitory dimerization X-ray crystallography at 1.8 Å, active-site and activation-loop mutagenesis Structure High 15893667
2005 CIB1, a 22-kDa Ca2+-binding protein, directly and specifically interacts with PAK1 within discrete regions surrounding the inhibitory switch domain in a calcium-dependent manner, activating PAK1 both in vitro and in vivo; CIB1 overexpression decreases cell migration through a PAK1/LIM kinase-dependent increase in cofilin phosphorylation; siRNA depletion of CIB1 reduces adhesion-induced PAK1 activation Pulldown, co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, cell migration assay The Journal of cell biology High 16061695
2005 PAK1 phosphorylates SHARP (a Notch signaling co-repressor) at Ser3486 and Thr3568 within its repression domain; this interaction enhances SHARP-mediated repression of Notch target genes; inhibition of PAK1 or mutation of phosphorylation sites abolishes SHARP co-repressor function Yeast two-hybrid, co-immunoprecipitation, in vitro phosphorylation with site mapping, reporter gene assay, PAK1 siRNA Oncogene High 15824732
2006 CRIPak is an endogenous PAK1 inhibitor that interacts with PAK1 through its N-terminal regulatory domain; CRIPak inhibits PAK1 kinase activity in vitro and in vivo, blocks PAK1-mediated LIMK activation and estrogen receptor transactivation; siRNA knockdown of CRIPak increases PAK1 activity and cytoskeletal remodeling Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, ER transactivation reporter Oncogene High 16278681
2006 PAK1 resides in a complex with atypical PKCζ and myosin II-B in an EGF-dependent manner; PAK1 is involved in aPKCζ phosphorylation, and aPKCζ in turn directly phosphorylates myosin II-B on a specific serine residue, leading to slower filament assembly of myosin II-B isoform specifically Co-immunoprecipitation, in vitro kinase assay, dominant-negative/knockdown experiments, myosin II-B filament assembly assay Molecular biology of the cell High 16611744
2007 Autophosphorylation of PAK1 triggered by Rho-family GTPase Chp leads to PAK1 ubiquitination and proteasomal degradation; Chp-induced degradation requires the PAK1 p21-binding domain, kinase activity, and autophosphorylation sites, but not PIX- or Nck-binding sites; Chp provides a function distinct from kinase activation to trigger PAK1 degradation Overexpression, ubiquitination assay, proteasome inhibitor treatment, domain mapping with deletion mutants, functional cell migration assay The Biochemical journal High 17355222
2004 Adhesion stimulates a direct physical association between PAK1 and ERK1/2; far-western analysis shows direct protein-protein interaction; peptide mapping identifies an ERK2-binding site within the PAK1 autoinhibitory domain; ERK2 phosphorylates PAK1 at Thr212 in vitro and in smooth muscle cells in an adhesion- and MEK/ERK-dependent manner; PAK-T212E phosphomimetic attenuates downstream ERK signaling, suggesting negative feedback Co-immunoprecipitation, far-western blotting, in vitro kinase assay, peptide mapping, phosphomimetic mutagenesis, reporter assay The Journal of biological chemistry High 15542607
2008 Pak1 depletion by siRNA interferes with heregulin-mediated dephosphorylation of cofilin and lamellipodial protrusion; Pak1 depletion decreases phospho-MLC levels whereas Pak2 depletion increases them, demonstrating isoform-specific opposite roles in MLC phosphorylation and focal adhesion maturation siRNA knockdown, western blot for cofilin and MLC phosphorylation, focal adhesion immunofluorescence, invasion assay Molecular and cellular biology High 18411304
2008 PAK1 directly interacts with dynein light chain LC8 via residues 212-222; NMR and crystallographic studies show PAK1 binds along the same groove as canonical LC8 partners but with a distinct hydrogen-bond network; LC8 binding interface requires LC8 dimerization and precludes phosphorylation of LC8 at Ser88; in vitro phosphorylation assays show activated PAK1 fails to phosphorylate LC8 X-ray crystallography, NMR, in vitro phosphorylation assay, LC8 point mutagenesis, biochemical binding assays The Journal of biological chemistry High 18650427
2009 A FRET-based conformational biosensor reveals PAK1 acquires an intermediate semi-open conformational state upon recruitment to the plasma membrane, selectively autophosphorylated on N-terminal serines but not Thr423; this intermediate is hypersensitive to Cdc42/Rac1 stimulation; PIX proteins contribute to PAK1 stimulation at membrane protrusions in a GTPase-independent way; trans-phosphorylation events occur between PAK1 molecules at the membrane FRET biosensor, live-cell imaging, pharmacological and genetic perturbations The Journal of biological chemistry High 19574218
2010 FOXO transcription factors directly regulate PAK1 gene expression as a transcriptional target; PAK1 acts locally in neuronal processes to induce polarity; knockdown of PAK1 phenocopies FOXO knockdown on neuronal polarity; exogenous PAK1 expression rescues polarity defects caused by FOXO knockdown in neurons in vivo Chromatin immunoprecipitation, shRNA knockdown, in vivo rescue experiments in rat cerebellar cortex, neuronal morphology analysis Genes & development High 20395366
2011 PAK1 is required for second/sustained-phase insulin secretion in pancreatic β-cells; PAK1 activation is Cdc42-dependent and signals downstream to activate ERK1/2; PAK1 knockout mice show whole-body glucose intolerance and peripheral insulin resistance; in skeletal muscle, PAK1 loss causes defective cofilin phosphorylation and impaired GLUT4 translocation PAK1 knockout mice, islet isolation and insulin secretion assay, glucose tolerance testing, GLUT4 translocation assay, western blot for ERK and cofilin phosphorylation The Journal of biological chemistry High 21969371
2012 CYK4 (part of the centralspindlin complex) acts as a GAP for Rac1 and inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways at the cell equator during cytokinesis; CYK4 GAP mutants show elevated PAK1 activity and defects in cytokinesis that are rescued by depletion of PAK1 or ARHGEF7 GAP mutant expression, Rac1 activity assay, PAK1/ARHGEF7 depletion rescue, immunofluorescence, cytokinesis phenotype scoring The Journal of cell biology High 22945935
2013 PAK1 can promote ERK/MEK activation in a kinase-independent manner; kinase-dead PAK1 overexpression increases MEK1/2 and ERK phosphorylation without affecting B-RAF or C-RAF Ser338 phosphorylation; activated Rac1 induces formation of a triple complex of Rac1, PAK1, and MEK1 independently of PAK1 kinase activity, suggesting a scaffold function for C-RAF interactions Kinase-dead PAK1 overexpression, western blot for downstream phosphorylation, co-immunoprecipitation of Rac1-PAK1-MEK1 complex The Journal of biological chemistry Medium 23653349
2013 HIV Nef recruits Pak1 and Pak2 to phosphorylate paxillin differentially: Pak1 phosphorylates paxillin at Ser258, which inhibits TACE/ADAM17 association and lipid raft transfer; Pak2 phosphorylates paxillin at Ser272/274 to induce TACE-paxillin association and extracellular vesicle shuttling Co-immunoprecipitation, site-specific phosphorylation mapping, extracellular vesicle fractionation, site-directed mutagenesis Molecular cell High 23317503
2014 A TrioGEF-Rac1-PAK1 signaling axis drives invadopodia disassembly; Rac1 FRET biosensor shows Rac1 activity is excluded from invadopodia cores and activated during disassembly; PAK1 downstream of Rac1 phosphorylates cortactin, causing invadopodia dissolution FRET biosensor, photoactivatable Rac1, pharmacological and genetic inhibition, cortactin phosphorylation analysis Nature cell biology High 24859002
2014 PAK1 inhibits nuclear translocation of Stat5 downstream of a FAK/Tiam1/Rac1/PAK1 pathway in FLT3- and KIT-driven leukemia cells; PAK1 inhibition prolongs survival of leukemic mice by blocking Stat5 nuclear translocation Pharmacological inhibition, shRNA knockdown, nuclear fractionation, mouse leukemia model survival analysis Cell reports Medium 25456130
2014 JAK2 kinase phosphorylates PAK1 on tyrosine residues in response to irradiation, which is essential for PAK1 protein stability and binding to Snail; this JAK2-PAK1-Snail pathway promotes EMT and radioresistance in lung cancer cells JAK2 inhibitor treatment, co-immunoprecipitation, phosphorylation western blot, PAK1 stability assay, EMT marker analysis, xenograft model Cancer research Medium 25125660
2014 Pak1 is required for ventricular Ca2+ homeostasis; cardiomyocyte-specific Pak1 deletion causes ventricular arrhythmias during β-adrenergic stress; Pak1 regulates SERCA2a expression through a transcriptional mechanism involving serum response factor (SRF); constitutively active Pak1 increases SERCA2a mRNA and protein Conditional cardiac Pak1 knockout, adenoviral overexpression, calcium imaging, electrophysiology, SERCA2a western blot and qPCR, SRF pathway analysis Circulation. Arrhythmia and electrophysiology High 25217043
2015 CK2α-interacting protein CKIP-1 mediates interaction between CK2α and PAK1 at membrane ruffles in a PI3K-dependent manner; PAK1 phosphorylation at Ser-223 by CK2 requires CKIP-1; PAK1 mediates phosphorylation of p41-Arc at the plasma membrane requiring PI3K and CKIP-1; CKIP-1 knockdown suppresses PAK1-mediated cell migration and invasion Co-immunoprecipitation, phosphorylation assays, siRNA knockdown, PI3K inhibition, cell migration/invasion assays The Journal of biological chemistry Medium 26160174
2016 GIT1/βPIX signaling proteins form complexes with γ-tubulin and PAK1 at centrosomes; depletion of PAK1 or inhibition of its kinase activity reduces microtubule nucleation from interphase centrosomes; in vitro kinase assays show GIT1 and βPIX (but not γ-tubulin) are PAK1 substrates; direct interaction of γ-tubulin with βPIX C-terminal domain and GIT1 N-terminal domain was demonstrated by pulldown Co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, microtubule regrowth assay, phenotypic rescue, pulldown Biochimica et biophysica acta High 27012601
2017 p27Kip1 promotes interaction of Cortactin with PAK1; PAK1 phosphorylates Cortactin to promote invadopodia turnover; Cortactin mutants at PAK1-targeted phosphorylation sites abolish p27's effect on invadopodia dynamics; in absence of p27, impaired PAK1-Cortactin interaction leads to increased invadopodia stability Co-immunoprecipitation, phospho-mutant expression, invadopodia dynamics assay, invasion assay, Rac1 pathway analysis eLife High 28287395
2018 De novo PAK1 mutations (Y131C, Y429C) reduce PAK1 dimerization as shown by co-immunoprecipitation and size-exclusion chromatography; reduced dimerization correlates with gain-of-function kinase activity; patient fibroblasts show enhanced phosphorylation of JNK, AKT, and c-JUN; PAK1 inhibitor FRAX486 reverses the filopodia-enriched cellular phenotype Co-immunoprecipitation, size-exclusion chromatography, phosphorylation western blot, cell spreading assay, PAK1 inhibitor rescue American journal of human genetics High 30290153
2018 RIT1 directly interacts with PAK1 as a novel effector; RIT1 also directly interacts with CDC42 and RAC1 independently of guanine nucleotide binding; the RIT1-PAK1 complex regulates actin cytoskeletal rearrangements (stress fiber dissolution, focal adhesion reduction); disease-causing RIT1 mutations enhance PAK1, CDC42, and RAC1 interactions; kinase-dead PAK1 prevents RIT1-mediated cytoskeletal effects Pulldown with purified recombinant proteins, co-immunoprecipitation, heterologous expression, cell morphology analysis, migration assay, kinase-dead rescue PLoS genetics High 29734338
2018 PAK1 loss in atrial myocytes increases Rac1 membrane translocation, enhances NOX2-dependent ROS production, and exaggerates AngII-induced intracellular Ca2+ increase leading to arrhythmic events via NCX activity; PAK1 stimulation (FTY720) attenuates NCX-dependent Ca2+ overload by suppressing NOX2-dependent ROS PAK1 knockout mice, AngII stimulation, NOX2 inhibitors, NCX inhibitors, Ca2+ imaging, electrophysiology, ROS measurement Heart rhythm High 29625277
2020 Hypoxia induces ELP3-mediated acetylation of PAK1 at K420, which suppresses PAK1 dimerization and enhances kinase activity; activated PAK1 phosphorylates ATG5 at T101, protecting it from ubiquitin-dependent degradation and increasing affinity of the ATG12-ATG5 complex for ATG16L1, promoting autophagosome formation; SIRT1-mediated deacetylation of PAK1 at K420 opposes this pathway Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, ubiquitination assay, autophagy flux assay, shRNA knockdown, inhibitor studies Autophagy High 32186433
2021 PP1A serves as the phosphatase in Smad4-mediated dephosphorylation of PAK1-T423; MYO18A acts as the PP1-interacting protein for substrate recognition; the Smad4-MYO18A-PP1A complex dephosphorylates PAK1-T423, thereby inhibiting PAK1-mediated β-catenin Ser675 phosphorylation and its nuclear translocation in cholangiocarcinoma LC-MS/MS, co-immunoprecipitation, in vitro phosphatase assay, domain mapping (RVFFR motif, CC domain), β-catenin localization, cell proliferation/invasion assays Cell death and differentiation High 34799729
2021 PAK1 promotes oligodendrocyte morphologic change and myelin production; inhibiting PAK1 early in oligodendrocyte development decreases morphologic complexity and alters F-actin spreading; constitutively activating AKT increases PAK1 expression; constitutively active PAK1 in zebrafish increases myelin internode length while PAK1 inhibition decreases it In vitro oligodendrocyte culture, PAK1 inhibitor treatment, constitutively active PAK1 expression in zebrafish, F-actin imaging, myelin internode measurement The Journal of neuroscience Medium 33478987
2022 Skeletal muscle PAK1 is required for insulin-stimulated GLUT4 vesicle translocation via a non-canonical pathway involving downstream effector ARPC1B; inducible skeletal muscle-specific PAK1 knockout impairs whole-body glucose homeostasis; PAK1-enriched muscle conditioned media enhances β-cell function, revealing tissue crosstalk Inducible muscle-specific knockout and overexpression mouse models, glucose/insulin tolerance testing, GLUT4-myc translocation assay, conditioned media experiments Frontiers in endocrinology High 35222279
2022 A PAK1-selective PROTAC degrader (BJG-05-039) using NVS-PAK1-1 allosteric inhibitor conjugated to lenalidomide induces selective PAK1 degradation via Cereblon E3 ubiquitin ligase; selective PAK1 degradation shows enhanced anti-proliferative effects relative to catalytic inhibition in PAK1-dependent but not PAK2-dependent cell lines PROTAC synthesis, protein degradation assay, anti-proliferation assay in PAK1 vs PAK2-dependent cell lines Journal of medicinal chemistry Medium 36416208
2023 Mechanical stress from fibrotic scarring induces PAK1-dependent nuclear softening and loss of H3K9Me3 heterochromatin repression; genetic loss of PAK1-dependent signaling impairs the mechanoadaptive response in vitro and dramatically improves fibrosis in liver and lung in vivo; PAK1 regulates actomyosin-dependent chromatin remodeling in myofibroblasts Genetic PAK1 manipulation, chromatin accessibility profiling (ATAC-seq), RNA-seq, nuclear mechanics assays, mouse liver and lung fibrosis models Cell reports Medium 37967011
1998 PAK1 is rapidly activated downstream of TCR signaling in a Lck-, Vav-, and Cdc42-dependent manner and associates with tyrosine-phosphorylated Nck; dominant-negative PAK1 or Nck specifically inhibits TCR-mediated NFAT activation and ERK2 activation but not JNK activation, placing Pak1 in a JNK-independent pathway for gene expression Co-immunoprecipitation, kinase activity assay, dominant-negative inhibition, NFAT and ERK reporter assays The EMBO journal High 9755165
2021 Fibrinogen activates PAK1 (phosphorylation) via syndecan-1, which in turn activates (dephosphorylates) cofilin, leading to disassembly of stress fibers and reduction of endothelial permeability; PAK1 silencing prevents fibrinogen-induced cofilin dephosphorylation and barrier protection Western blot for PAK1 and cofilin phosphorylation, siRNA knockdown, FITC-dextran permeability assay, in vivo hemorrhagic shock model Shock Medium 32433215

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nature cell biology 862 10559936
1995 Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. The Journal of biological chemistry 676 7592586
1997 Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Current biology : CB 609 9395435
1999 p21-activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts. The Journal of cell biology 332 10330410
1996 Interaction of the Nck adapter protein with p21-activated kinase (PAK1). The Journal of biological chemistry 273 8824201
1997 Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. The Journal of cell biology 200 9298982
2011 Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells. Proceedings of the National Academy of Sciences of the United States of America 172 21482786
2020 Hypoxia-induced acetylation of PAK1 enhances autophagy and promotes brain tumorigenesis via phosphorylating ATG5. Autophagy 137 32186433
2000 Temporal and spatial distribution of activated Pak1 in fibroblasts. The Journal of cell biology 137 11134074
2014 A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly. Nature cell biology 134 24859002
2003 Yeast Pak1 kinase associates with and activates Snf1. Molecular and cellular biology 124 12748292
2007 Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer. Oncogene 122 17486065
2011 Inhibition or ablation of p21-activated kinase (PAK1) disrupts glucose homeostatic mechanisms in vivo. The Journal of biological chemistry 117 21969371
2002 Association of PI-3 kinase with PAK1 leads to actin phosphorylation and cytoskeletal reorganization. Molecular biology of the cell 110 12181358
2008 Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms. Molecular and cellular biology 108 18411304
2003 Intracellular localization and functional effects of P21-activated kinase-1 (Pak1) in cardiac myocytes. Circulation research 107 14670848
2001 Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. The Journal of biological chemistry 106 11733498
1998 A Nck-Pak1 signaling module is required for T-cell receptor-mediated activation of NFAT, but not of JNK. The EMBO journal 105 9755165
2021 DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. The Journal of clinical investigation 104 33945512
2001 Etk/Bmx tyrosine kinase activates Pak1 and regulates tumorigenicity of breast cancer cells. The Journal of biological chemistry 97 11382770
2012 CYK4 inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways during cytokinesis. The Journal of cell biology 90 22945935
2006 PAK1 and aPKCzeta regulate myosin II-B phosphorylation: a novel signaling pathway regulating filament assembly. Molecular biology of the cell 89 16611744
2003 p21-activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple to growth factor signaling. The Journal of biological chemistry 87 12522133
2013 HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Molecular cell 85 23317503
2017 MicroRNA-494 inhibits breast cancer progression by directly targeting PAK1. Cell death & disease 80 28055013
2010 A FOXO-Pak1 transcriptional pathway controls neuronal polarity. Genes & development 79 20395366
2005 The active conformation of the PAK1 kinase domain. Structure (London, England : 1993) 75 15893667
2014 PAK1 tyrosine phosphorylation is required to induce epithelial-mesenchymal transition and radioresistance in lung cancer cells. Cancer research 74 25125660
2017 Targeting PAK1. Biochemical Society transactions 72 28202661
2013 P21-activated kinase 1 (PAK1) as a therapeutic target in BRAF wild-type melanoma. Journal of the National Cancer Institute 72 23535073
2005 Essential role of CIB1 in regulating PAK1 activation and cell migration. The Journal of cell biology 71 16061695
2010 Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer. BMC cancer 70 20426825
2003 Role of the serine-threonine kinase PAK-1 in myxoma virus replication. Journal of virology 70 12719581
2020 PAK1-blockers: Potential Therapeutics against COVID-19. Medicine in drug discovery 69 32313880
2004 PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Molecular biology of the cell 69 15282344
2013 p21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner. The Journal of biological chemistry 62 23653349
2018 Activating Mutations in PAK1, Encoding p21-Activated Kinase 1, Cause a Neurodevelopmental Disorder. American journal of human genetics 61 30290153
2007 Pak1 regulates dendritic branching and spine formation. Developmental neurobiology 58 17443815
2014 miR-145 inhibits invasion of bladder cancer cells by targeting PAK1. Urologic oncology 57 24954107
2015 miR-30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy. Cardiovascular therapeutics 56 25781190
2004 Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. The Journal of biological chemistry 55 15542607
2015 PAK1 is a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome. Blood 53 26170031
2014 Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis. Cell reports 51 25456130
2015 Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer. Inflammatory bowel diseases 50 25569743
2014 Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer. Molecular cancer 49 25174975
2007 Autophosphorylation-dependent degradation of Pak1, triggered by the Rho-family GTPase, Chp. The Biochemical journal 49 17355222
2014 Erk5 inhibits endothelial migration via KLF2-dependent down-regulation of PAK1. Cardiovascular research 48 25388666
2016 FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine. BMC cancer 47 26774265
2014 PAK1 mediates pancreatic cancer cell migration and resistance to MET inhibition. The Journal of pathology 47 25074413
2020 Desmoglein-2 modulates tumor progression and osimertinib drug resistance through the EGFR/Src/PAK1 pathway in lung adenocarcinoma. Cancer letters 46 32272148
2015 PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion. Cell death & disease 45 25766321
2012 PAK1-dependent MAPK pathway activation is required for colorectal cancer cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 45 22252525
2008 The Pak1 kinase: an important regulator of neuronal morphology and function in the developing forebrain. Molecular neurobiology 45 18649038
2008 Biochemical and structural characterization of the Pak1-LC8 interaction. The Journal of biological chemistry 44 18650427
2017 p27Kip1 promotes invadopodia turnover and invasion through the regulation of the PAK1/Cortactin pathway. eLife 43 28287395
2006 CRIPak, a novel endogenous Pak1 inhibitor. Oncogene 43 16278681
2023 Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK. Biophysical reviews 42 37124926
2019 Inhibition of PAK1 suppresses pancreatic cancer by stimulation of anti-tumour immunity through down-regulation of PD-L1. Cancer letters 42 31857154
2018 microRNA-96 protects pancreatic β-cell function by targeting PAK1 in gestational diabetes mellitus. BioFactors (Oxford, England) 41 30536654
2021 The Smad4-MYO18A-PP1A complex regulates β-catenin phosphorylation and pemigatinib resistance by inhibiting PAK1 in cholangiocarcinoma. Cell death and differentiation 40 34799729
2016 P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer. Annals of oncology : official journal of the European Society for Medical Oncology 40 27117533
2017 The p21-activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration. British journal of pharmacology 38 28574147
2005 An essential role of Pak1 phosphorylation of SHARP in Notch signaling. Oncogene 38 15824732
2019 De novo variants in PAK1 lead to intellectual disability with macrocephaly and seizures. Brain : a journal of neurology 37 31504246
2016 microRNA-7 regulates cell growth, migration and invasion via direct targeting of PAK1 in thyroid cancer. Molecular medicine reports 37 27430434
2009 Dissecting activation of the PAK1 kinase at protrusions in living cells. The Journal of biological chemistry 37 19574218
2019 lncRNA MALAT1 potentiates the progression of tongue squamous cell carcinoma through regulating miR-140-5p-PAK1 pathway. OncoTargets and therapy 36 30863103
2013 Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 24347489
2005 PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis. Cellular signalling 35 15993754
2014 Pak1 is required to maintain ventricular Ca²⁺ homeostasis and electrophysiological stability through SERCA2a regulation in mice. Circulation. Arrhythmia and electrophysiology 34 25217043
2016 Pharmacological inhibition of Rac1-PAK1 axis restores tamoxifen sensitivity in human resistant breast cancer cells. Cellular signalling 33 27939839
2019 PAK1 promotes proliferation, migration and invasion of hepatocellular carcinoma by facilitating EMT via directly up-regulating Snail. Genomics 32 31071459
2020 circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis. Cancer gene therapy 31 32855541
2019 MiR-142-3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer. Journal of cellular physiology 31 31674013
2005 Spatiotemporal regulation of the Pak1 kinase. Biochemical Society transactions 31 16042564
2019 Identification of a novel PAK1 inhibitor to treat pancreatic cancer. Acta pharmaceutica Sinica. B 30 32322465
2021 PAK1 Positively Regulates Oligodendrocyte Morphology and Myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 33478987
2015 PAK1 regulates cortical development via promoting neuronal migration and progenitor cell proliferation. Molecular brain 29 26043730
2018 RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1. PLoS genetics 28 29734338
2021 p21-Activated kinase 1 (PAK1) in aging and longevity: An overview. Ageing research reviews 25 34390849
2020 MiR-26a/miR-26b represses tongue squamous cell carcinoma progression by targeting PAK1. Cancer cell international 25 32190006
2020 Fission yeast Pak1 phosphorylates anillin-like Mid1 for spatial control of cytokinesis. The Journal of cell biology 25 32421151
2016 GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation. Biochimica et biophysica acta 25 27012601
2018 Loss of p21-activated kinase 1 (Pak1) promotes atrial arrhythmic activity. Heart rhythm 24 29625277
2003 Pak1 and its T212 phosphorylated form accumulate in neurones and epithelial cells of the developing rodent. Developmental dynamics : an official publication of the American Association of Anatomists 24 12950086
2024 Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases. Histopathology 22 38785043
2022 Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis. Frontiers in endocrinology 22 35222279
2018 NCK1 promotes the angiogenesis of cervical squamous carcinoma via Rac1/PAK1/MMP2 signal pathway. Gynecologic oncology 22 30442385
2019 Effect of P21-activated kinase 1 (PAK-1) inhibition on cancer cell growth, migration, and invasion. Pharmacology research & perspectives 21 31516713
2023 The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation. Cell death & disease 20 37225681
2015 The Role of the Pleckstrin Homology Domain-containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1). The Journal of biological chemistry 20 26160174
2013 PAK1-deficiency/down-regulation reduces brood size, activates HSP16.2 gene and extends lifespan in Caenorhabditis elegans. Drug discoveries & therapeutics 20 23524941
2019 PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions. Scientific reports 19 31748572
2020 Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma. Journal of cellular and molecular medicine 18 32237037
2023 Modulation of Rac1/PAK1/connexin43-mediated ATP release from astrocytes contributes to retinal ganglion cell survival in experimental glaucoma. Glia 17 36794533
2023 PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis. Cell reports 17 37967011
2021 Fibrinogen Activates PAK1/Cofilin Signaling Pathway to Protect Endothelial Barrier Integrity. Shock (Augusta, Ga.) 17 32433215
2016 P21 (Cdc42/Rac)-activated kinase 1 (pak1) is associated with cardiotoxicity induced by antihistamines. Archives of pharmacal research 17 27681411
2013 Depletion of PAK1 enhances ubiquitin-mediated survivin degradation in pancreatic β-cells. Islets 17 23514967
2022 Development and Utility of a PAK1-Selective Degrader. Journal of medicinal chemistry 16 36416208