Affinage

PAK1

Serine/threonine-protein kinase PAK 1 · UniProt Q13153

Length
545 aa
Mass
60.6 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 48 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

PAK1 is a Cdc42/Rac1-activated serine/threonine kinase that couples upstream GTPase and growth-factor signals to actin-cytoskeleton remodeling, directional cell motility, and downstream MAPK cascades (PMID:9395435, PMID:10330410, PMID:9234703). In its basal state PAK1 forms autoinhibited trans homodimers in which the N-terminal regulatory domain of one molecule blocks the catalytic domain of its partner; GTP-loaded Cdc42 or Rac1 dissociates the dimer to relieve inhibition (PMID:11804587), and full activation at membrane protrusions proceeds through a two-step conformational mechanism in which membrane recruitment produces a semi-open state with N-terminal serine autophosphorylation followed by GTPase-stimulated activation-loop phosphorylation (PMID:19574218). The activation loop is phosphorylated on Thr423 by PDK1 in trans (PMID:10995762), while membrane recruitment and activation also depend on the adaptor Nck, which links PAK1 through its second SH3 domain to receptor tyrosine kinases such as EGFR and PDGFR (PMID:8824201, PMID:8798379); tyrosine kinases including JAK2 further phosphorylate PAK1 to augment its activity (PMID:17726028). Once active, PAK1 drives polarized lamellipodia, filopodia, and directed migration through phosphorylation of myosin light chain, cofilin, and non-muscle myosin II-B (PMID:9395435, PMID:10330410, PMID:15993754), and it regulates invadopodia turnover by phosphorylating cortactin downstream of a Trio–Rac1 axis (PMID:24859002, PMID:28287395). PAK1 directly binds and phosphorylates Raf-1 on Ser338 to activate the MEK/ERK cascade and is required for Ras-induced JNK and ERK activation and cellular transformation (PMID:11733498, PMID:9234703, PMID:18940914). Through a broad substrate repertoire—including β-catenin (Ser675), MORC2 (Ser677), FKHR, vimentin, and the centrosomal regulators GIT1 and βPIX—PAK1 controls proliferation, transcription, intermediate-filament assembly, and microtubule nucleation (PMID:23576562, PMID:25888627, PMID:12560069, PMID:32389644, PMID:27012601). Physiologically, PAK1 governs neuronal and epithelial polarity, the latter acting as a redundant apical-determining kinase alongside aPKC downstream of Cdc42 (PMID:20395366, PMID:29444419), cortical neurogenesis (PMID:26043730), insulin-stimulated GLUT4 translocation and glucose homeostasis in muscle and β-cells (PMID:21969371, PMID:35222279), and cardiac myofilament Ca2+ sensitivity via association with PP2A (PMID:14670848). De novo gain-of-function PAK1 mutations (Y131C, Y429C) that reduce homodimerization and elevate kinase activity cause a developmental disorder with elevated JNK/AKT/c-JUN signaling and a filopodia-enriched cell-spreading phenotype (PMID:30290153).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Established how PAK1 is physically recruited downstream of growth-factor receptors, answering how an effector kinase connects to RTK signaling.

    Evidence Co-IP in COS-7/Swiss 3T3, in vitro binding, kinase assays, and SH3-domain mapping linking Nck to the PAK1 N-terminal proline-rich motif and to EGFR/PDGFR

    PMID:8798379 PMID:8824201

    Open questions at the time
    • Did not resolve how Nck binding is coordinated with GTPase-mediated activation
    • Functional consequence of PAK1 phosphorylation of Nck unclear
  2. 1997 High

    Demonstrated PAK1 is sufficient to reorganize the actin cytoskeleton and that its cytoskeletal effects can be GTPase-binding-independent, establishing PAK1 as an actin-remodeling effector.

    Evidence Microinjection of activated PAK1 and domain/SH3-binding mutants into Swiss 3T3 cells with actin immunofluorescence; kinase-dead and GTPase-binding mutant epistasis in Rat-1 Ras-transformation assays

    PMID:9234703 PMID:9395435

    Open questions at the time
    • Direct cytoskeletal substrates not identified in these studies
    • Relative contributions of kinase activity vs scaffolding to morphology not separated
  3. 1999 High

    Showed PAK1 kinase activity is required for directional (not just random) motility via MLC phosphorylation, distinguishing PAK1's role in cell guidance.

    Evidence Tetracycline-inducible WT/CA/kinase-dead PAK1 with motility assays on ECM gradients and MLC phospho-immunoblot

    PMID:10330410

    Open questions at the time
    • Whether MLC is a direct PAK1 substrate vs indirect not resolved
    • Spatial dynamics of activation during migration not addressed
  4. 2000 High

    Identified PDK1 as the activation-loop kinase phosphorylating PAK1 Thr423, defining a key upstream activating input independent of PI3K.

    Evidence Reconstituted in vitro kinase assay with purified PDK1/PAK1, T423 mutagenesis, phospho-T423 antibody, and co-IP

    PMID:10995762

    Open questions at the time
    • Physiological signals controlling PDK1–PAK1 engagement not defined
    • Role of sphingosine cofactor in vivo unclear
  5. 2001 High

    Placed PAK1 directly upstream of Raf-1 activation, mechanistically linking PAK1 to the ERK cascade.

    Evidence Reciprocal Co-IP with conformation-dependent binding, domain mapping, in vitro Raf-1 Ser338 phosphorylation, and MAPK readouts; spatial activation at the leading edge via phospho-T423 antibody

    PMID:11134074 PMID:11733498

    Open questions at the time
    • How PAK1 N-terminal regulatory inhibition of Raf binding is relieved in vivo not detailed
    • Other RTK kinases regulating leading-edge activation not fully mapped
  6. 2002 High

    Resolved the autoinhibition mechanism: PAK1 dimerizes in trans and GTPase binding dissociates the dimer, explaining how Cdc42/Rac1 activate the kinase.

    Evidence Crystal structure of the autoinhibited dimer plus in vivo Co-IP and GTPase activation assays

    PMID:11804587

    Open questions at the time
    • How βPIX association with dimers modulates activation not resolved here
    • Membrane context of dimer dissociation not captured by crystallography
  7. 2007 High

    Defined tyrosine phosphorylation as an activating input, with JAK2 phosphorylating specific tyrosines required for PAK1's survival and motility functions.

    Evidence In vitro JAK2 kinase assay with MS site mapping (Y153/Y201/Y285), phospho-dead mutagenesis, and apoptosis/motility readouts; complementary Etk/Bmx tyrosine phosphorylation

    PMID:11382770 PMID:17726028

    Open questions at the time
    • Crosstalk between tyrosine and serine/threonine activation modes unresolved
    • Stoichiometry and ordering of phosphorylation events unknown
  8. 2009 High

    Defined the spatial, two-step conformational activation of PAK1 at protrusions, reconciling membrane recruitment, autophosphorylation, and GTPase input.

    Evidence PAK1-FRET conformational biosensor in live cells with pharmacological/genetic perturbation

    PMID:19574218

    Open questions at the time
    • Identity of the membrane recruitment trigger for the semi-open state not fully defined
  9. 2013 High

    Expanded the PAK1 substrate repertoire into transcriptional and oncogenic control by identifying β-catenin Ser675 and MORC2 Ser677 as functional substrates.

    Evidence In vitro kinase assays with phospho-mimetic rescue, PAK1 KO in MMTV-ErbB2 mice and xenografts; HIV Nef-driven paxillin Ser258 phosphorylation distinguishing PAK1 from PAK2

    PMID:23317503 PMID:23576562 PMID:25888627

    Open questions at the time
    • In vivo phosphorylation stoichiometry of β-catenin/MORC2 not quantified
    • Isoform-specific substrate selectivity mechanism not defined
  10. 2014 High

    Established PAK1 as a driver of invadopodia disassembly via cortactin phosphorylation, clarifying its role in invasion dynamics.

    Evidence Rac1-FRET biosensor with photoactivation, Trio/Rac1/PAK1 knockdown, cortactin phospho-assays; p27Kip1-dependent PAK1–cortactin coupling

    PMID:24859002 PMID:28287395

    Open questions at the time
    • How PAK1 is spatially restricted relative to invadopodia cores not fully defined
    • Balance between assembly and disassembly outputs context-dependent
  11. 2011 High

    Established PAK1 as an in vivo regulator of glucose homeostasis through insulin secretion and GLUT4 translocation with tissue-specific downstream wiring.

    Evidence PAK1-/- and muscle-specific inducible KO/OE mice with glucose/insulin tolerance, GLUT4 translocation, cofilin/ERK readouts, and conditioned-media crosstalk; β-cell Survivin stability assays

    PMID:21969371 PMID:23514967 PMID:35222279

    Open questions at the time
    • Direct PAK1 substrate driving GLUT4 vesicle translocation not identified
    • Nature of the secreted muscle-to-β-cell crosstalk factor unknown
  12. 2018 High

    Connected PAK1 to human disease and to conserved polarity control, defining gain-of-function mutations and a redundant apical-determining role with aPKC.

    Evidence Patient fibroblasts with dimerization/kinase/phospho-signaling assays and pharmacological rescue; Drosophila/mammalian double-inactivation with in vitro polarity substrate kinase assays

    PMID:29444419 PMID:30290153

    Open questions at the time
    • Full spectrum of disease-causing alleles and tissue-level phenotypes not enumerated
    • Shared polarity substrates of PAK1 and aPKC not individually validated in vivo
  13. 2021 High

    Broadened PAK1's physiological roles into sensory, cardiac, vascular, and chromatin-mechanotransduction contexts.

    Evidence PAK1-/- mice with hearing/stereocilia and atrial arrhythmia phenotypes; cofilin/ERM/spectrin and NOX2/NCX readouts; ATAC-seq/H3K9Me3 mechanoadaptation in fibrosis models

    PMID:29625277 PMID:34049799 PMID:37967011

    Open questions at the time
    • Direct mechanotransduction substrate linking PAK1 to chromatin softening not identified
    • Tissue-specific upstream activators in these contexts not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple activating inputs (GTPases, PDK1, tyrosine kinases, membrane recruitment) are integrated quantitatively and spatially to select among PAK1's divergent downstream outputs remains unresolved.
  • No unified model relating activation mode to substrate selection
  • Isoform-specific (PAK1 vs PAK2) substrate determinants incompletely defined
  • In vivo phosphorylation site occupancy across tissues unmeasured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 5 GO:0008092 cytoskeletal protein binding 4 GO:0140110 transcription regulator activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 2
Partners
ARHGEF7CDC42FLNAGIT1NCK1PPP2CARAC1RAF1
Complex memberships
PAK1 homodimerPAK1–βPIX–GIT1 complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Activated PAK1 microinjected into quiescent Swiss 3T3 cells rapidly induces polarized filopodia and membrane ruffles; PAK1 amino-terminal mutants unable to bind Cdc42/Rac1 drive actin accumulation in large polarized ruffles and focal complexes. Enhanced binding to the adaptor protein Nck (via SH3 domains) mediates these cytoskeletal effects, and mutation of a proline in the SH3-binding region abolishes them. Microinjection of activated protein; overexpression of domain mutants; SH3-binding mutagenesis; immunofluorescence actin staining Current Biology High 9395435
1996 PAK1 physically interacts with the adaptor protein Nck in vivo (COS-7 and Swiss 3T3 cells). The interaction is mediated by the second SH3 domain of Nck binding to the first proline-rich motif at the PAK1 N-terminus. Active PAK1 phosphorylates Nck at multiple sites upon association. The interaction is strengthened by PDGF receptor stimulation. Co-immunoprecipitation in vivo; in vitro binding assays; phosphorylation assay; domain mapping with SH3-domain constructs The Journal of Biological Chemistry High 8798379 8824201
1996 Nck links receptor tyrosine kinases (EGFR, PDGFR) to PAK1 via its second SH3 domain. PAK1 kinase activity is increased in response to EGF in HeLa cells, and co-transfection of Nck enhances PAK1 activity, positioning PAK1 as a downstream effector of growth factor receptors. Co-immunoprecipitation; transient transfection; in vitro kinase assay after EGF stimulation The Journal of Biological Chemistry High 8798379
1999 PAK1 kinase activity is required for directional cell motility. Constitutively active PAK1 increases myosin light chain (MLC) phosphorylation and promotes polarized lamellipodia and directed movement, whereas kinase-dead PAK1 fails to increase MLC phosphorylation and causes multi-directional lamellipodia with impaired directional motility. Effects on actin organization are not blocked by dominant-negative Rac1. Tetracycline-inducible expression of wild-type, constitutively active, and kinase-dead PAK1; F-actin imaging; motility assays on fibronectin/collagen gradients; MLC phosphorylation immunoblot The Journal of Cell Biology High 10330410
2000 PDK1 phosphorylates PAK1 on threonine 423 within the activation loop (kinase subdomain VIII) in the presence of sphingosine, increasing PAK1 catalytic activity. Threonine 423 phosphorylation by PDK1 occurs independently of PI3-kinase/wortmannin-sensitive pathways. Phosphorylation of T423 occurs by an intermolecular (trans) mechanism and PDK1 interacts with PAK1 in vivo. In vitro kinase assay with purified PDK1 and PAK1; phosphatase pretreatment; phospho-T423-specific antibody; site-directed mutagenesis (T423); co-immunoprecipitation in COS-7 cells The Journal of Biological Chemistry High 10995762
2002 PAK1 forms homodimers in vivo that are autoinhibited in trans: the N-terminal inhibitory domain of one PAK1 molecule binds and inhibits the catalytic domain of the partner. GTP-Cdc42 or GTP-Rac1 binding dissociates the dimer, activating both partners. The adaptor βPIX can stably associate with dimerized PAK1. Dimerization does not facilitate trans-phosphorylation between PAK1 molecules. Crystal structure of autoinhibited PAK1 dimer; co-immunoprecipitation of dimerized PAK1 in vivo; GTPase-binding assays; domain mutagenesis Molecular Cell High 11804587
2001 PAK1 directly associates with Raf-1 and phosphorylates Raf-1 on Ser338, a step required for Raf-1 activation. The interaction depends on the active conformation of both PAK1 and Raf-1; kinase-dead PAK1 barely binds Raf. The Raf-1 binding site maps to the C-terminus of the PAK1 catalytic domain, and the PAK1 N-terminal regulatory region inhibits this interaction. Co-immunoprecipitation under physiological and overexpressed conditions; active mutant and kinase-dead PAK1 constructs; in vitro phosphorylation of Raf-1 Ser338; MAPK activation assays The Journal of Biological Chemistry High 11733498
2000 Activated PAK1 localizes to focal adhesion sites, filopodia, and lamellipodia edges in NIH-3T3 cells expressing activated Cdc42 or Rac1. During wound closure, PAK1 is rapidly activated at the leading edge of motile cells; this activation requires PI3-kinase and Src-family kinase activity but not EGFR activity. Phospho-specific anti-pT423 PAK1 antibody for immunofluorescence; live-cell wound-closure assay; pharmacological inhibitors of PI3K, Src, and EGFR The Journal of Cell Biology High 11134074
1997 Kinase-dead PAK1 (R299 mutation) inhibits Ras transformation of Rat-1 fibroblasts by ~90–95% but not Raf-induced transformation. A PAK1 mutant that cannot bind Rac/Cdc42 also inhibits Ras transformation. Rac/Ras activation of JNK is inhibited by kinase-dead PAK1 but not by the Rac/Cdc42-binding-deficient mutant; Ras activation of ERK is inhibited by both mutants. Cotransfection transformation assay in Rat-1 cells; Pak1 mutants defective in GTPase binding or kinase activity; JNK and ERK activity assays Molecular and Cellular Biology High 9234703
2003 PAK1 physically interacts with protein phosphatase 2A (PP2A) in cardiac myocytes. Constitutively active PAK1 reduces phosphorylation of cardiac troponin I (cTnI) and myosin binding protein C (C-protein), leading to increased myofilament Ca2+ sensitivity. PAK1 localizes to the Z-disk, cell membrane, intercalated disc, and nuclear membrane in adult rat cardiomyocytes. Adenoviral expression of constitutively active PAK1; co-immunoprecipitation with PP2A; immunofluorescence localization; phosphorylation of cTnI and C-protein by immunoblot; Ca2+-tension relation measurements in single myocytes Circulation Research High 14670848
2001 Etk/Bmx tyrosine kinase directly associates with PAK1 via its N-terminal pleckstrin homology domain and phosphorylates PAK1 on tyrosine residues, identifying tyrosine phosphorylation as a regulatory mechanism for PAK1. Transient transfection; co-immunoprecipitation; GST pull-down assay; in vitro tyrosine phosphorylation The Journal of Biological Chemistry Medium 11382770
2007 JAK2 tyrosine kinase directly phosphorylates PAK1 on tyrosines 153, 201, and 285, identified by mass spectrometry and 2D peptide mapping. Tyrosyl phosphorylation by JAK2 significantly increases PAK1 kinase activity. Mutation of these three tyrosines to phenylalanines abolishes JAK2-induced PAK1 activation, apoptosis protection, and increase in cell motility. In vitro kinase assay (wild-type vs. kinase-dead JAK2); mass spectrometry; 2D peptide mapping; site-directed mutagenesis (Y153F, Y201F, Y285F); PAK1 activity assays; apoptosis and motility assays The Journal of Biological Chemistry High 17726028
2003 Estrogen directly activates PAK1 kinase activity in mammary cancer cells in a PI3K-independent manner. Active PAK1 directly interacts with and phosphorylates the forkhead transcription factor FKHR, causing its perinuclear/cytoplasmic localization and preventing FKHR-dependent transcription of Fas ligand. Dominant-negative PAK1 autoinhibitory domain (aa 83–149) reverses this effect. In vitro PAK1 kinase assay after estrogen treatment; co-immunoprecipitation of PAK1-FKHR; immunofluorescence of FKHR localization; FRE-luciferase reporter assay FEBS Letters Medium 12560069
2006 CRIPak, a cysteine-rich protein identified by yeast two-hybrid screen of a mammary gland library, binds PAK1 via the N-terminal regulatory domain and inhibits PAK1 kinase activity both in vitro and in vivo. CRIPak inhibits PAK1-mediated LIM kinase activation and PAK1-dependent ER transactivation. Hormonal stimulation promotes CRIPak colocalization with ER in the nucleus. Yeast two-hybrid; co-immunoprecipitation; in vitro and in vivo kinase assays; siRNA knockdown of CRIPak; immunofluorescence colocalization Oncogene Medium 16278681
2004 PAK1 directly associates with ERK1/2 via a binding site within the PAK1 autoinhibitory domain. ERK2 phosphorylates PAK1 on Thr212 in vitro and in smooth muscle cells following PDGF treatment in an adhesion- and MEK/ERK-dependent manner. PAK1-T212E (phospho-mimetic) markedly attenuates downstream ERK signaling. Deletion of the ERK-binding site in PAK1 reduces ERK-dependent SRE-luciferase reporter activity. Co-immunoprecipitation; far-Western (direct protein-protein interaction); peptide mapping; in vitro ERK2 kinase assay with PAK1; phospho-mimetic and deletion mutants; SRE-luciferase reporter The Journal of Biological Chemistry High 15542607
2006 Nuclear localization of PAK1 is required for tamoxifen resistance in breast cancer. PAK1 lacking functional nuclear localization signals (PAK1ΔNLS) fails to stimulate cyclin D1 expression or compromise tamoxifen response in MCF-7 cells, whereas wild-type PAK1 does. Tamoxifen treatment increases nuclear PAK1 and PAK1 kinase activity in endometrial cancer cells. Inducible constitutively active PAK1; transient overexpression of Wt-PAK1 and PAK1ΔNLS; cyclin D1 promoter-luciferase reporter; immunofluorescence; kinase activity assay Journal of the National Cancer Institute Medium 16705121
2009 PAK1 activation at protrusions requires a two-step conformational mechanism: (1) membrane recruitment induces a semi-open intermediate state selectively autophosphorylated on N-terminal serines but not T423; (2) full activation requiring T423 phosphorylation is stimulated by Cdc42/Rac1. βPIX interaction contributes to PAK1 stimulation at membrane protrusions in a GTPase-independent manner. Trans-phosphorylation events occur between PAK1 molecules at the membrane. FRET conformational biosensor (PAK1-FRET) in live COS-7 and NRK cells; pharmacological inhibitors; GTPase expression; domain mutants The Journal of Biological Chemistry High 19574218
2008 PAK1 activates ERK1/2 to regulate lamellipodial dynamics. PAK1-null macrophages show reduced MAPK activation by CSF1 and form more, but less stable, lamellipodia after adhesion. Pharmacological inhibition of ERK1/2 in wild-type macrophages phenocopies PAK1 loss (increased spread area, unstable lamellipodia), placing ERK downstream of PAK1 in this pathway. PAK1-/- mouse-derived macrophages; ERK1/2 activity assay; ERK1/2 inhibitor; live-cell imaging of lamellipodial dynamics Journal of Cell Science High 18940914
2011 PAK1 is required for second/sustained-phase insulin secretion in pancreatic beta cells (dependent on Cdc42 abundance upstream) and for GLUT4 translocation in skeletal muscle downstream of insulin. In beta cells, PAK1 signals to ERK1/2 activation; in skeletal muscle, PAK1 signals via cofilin phosphorylation (but not ERK1/2). PAK1-/- mice exhibit whole-body glucose intolerance and peripheral insulin resistance. PAK1-/- knockout mice; glucose tolerance test; insulin tolerance test; GLUT4 translocation assay; cofilin and ERK1/2 phosphorylation by immunoblot; PAK1 inhibitor IPA3 on human islets The Journal of Biological Chemistry High 21969371
2013 PAK1 directly phosphorylates β-catenin at Ser675, stabilizing β-catenin and driving expression of β-catenin target genes during ErbB2-induced mammary transformation. Loss of PAK1, but not PAK2, reduces β-catenin levels. A phospho-mimetic S675E β-catenin mutant rescues transformation in PAK1-deficient ErbB2-positive cells. PAK1 knockout in MMTV-ErbB2 transgenic mice; in vitro PAK1 kinase assay on β-catenin; phospho-mimetic S675E β-catenin rescue; small-molecule PAK and β-catenin inhibitors in xenograft model Cancer Research High 23576562
2013 HIV Nef activates a paxillin/TACE pathway in which Pak1 phosphorylates paxillin on Ser258, which inhibits TACE-paxillin association and lipid raft transfer (opposite to Pak2, which phosphorylates paxillin Ser272/274 to promote TACE shuttling into extracellular vesicles). In vitro kinase assay; site-directed mutagenesis of paxillin (Ser258, Ser272/274); co-immunoprecipitation; lipid raft fractionation; extracellular vesicle analysis Molecular Cell High 23317503
2014 A Trio GEF–Rac1–Pak1 signaling axis drives invadopodia disassembly. Active Rac1 (measured by FRET biosensor) is excluded from invadopodia cores and increases upon disassembly. Pak1 phosphorylates cortactin downstream of Rac1, and this phosphorylation causes invadopodia dissolution. Single-chain Rac1-FRET biosensor; Rac1 photoactivation at invadopodia; TrioGEF, Rac1, Pak1 knockdown; cortactin phosphorylation assays; invasion assays Nature Cell Biology High 24859002
2003 In Saccharomyces cerevisiae, yeast Pak1 kinase associates with and phosphorylates Snf1 kinase on threonine 210 within the activation loop, activating the Snf1 complex (specifically the Snf1-Gal83 form). The Pak1-Snf1 association is enhanced under glucose-limiting conditions. Pak1 catalytic activity is also required for nuclear enrichment of the Snf1-Gal83 complex in response to carbon stress. Co-immunoprecipitation in vivo; in vitro kinase assay with purified Pak1; phosphorylation of Snf1-T210 in vitro and in vivo; genetic epistasis (pak1Δ suppresses reg1Δ phenotypes); Snf1-GFP localization Molecular and Cellular Biology High 12748292
2008 PAK1 (residues 212–222) binds to LC8 dynein light chain along the same canonical target-binding groove formed by LC8 dimerization. The target-binding interface requires LC8 dimerization. LC8 Ser88, previously proposed as a PAK1 phosphorylation site, is inaccessible in the dimer; in vitro phosphorylation assays with activated PAK1 fail to phosphorylate LC8, thus refuting the model that PAK1 phosphorylates LC8 to promote anchorage-independent growth. NMR; X-ray crystallography; in vitro kinase assay; LC8 point mutants (K36P, T67A); biochemical binding assays The Journal of Biological Chemistry High 18650427
2010 FOXO transcription factors directly transcribe the Pak1 gene; Pak1 acts locally in neuronal processes to establish axo-dendritic polarity. Pak1 knockdown phenocopies FOXO knockdown in hippocampal and cerebellar neurons. Re-expression of Pak1 in the FOXO-knockdown background restores neuronal polarity in primary neurons and postnatal rat pups in vivo. Knockdown of FOXO proteins and Pak1 by RNAi in primary neurons and in vivo; rescue with exogenous Pak1; chromatin immunoprecipitation and reporter assays for Pak1 as FOXO target gene Genes & Development High 20395366
2012 During cytokinesis, the centralspindlin component CYK4 acts as a GAP for Rac1 at the cell equator in anaphase, suppressing Rac1-dependent effector pathways including PAK1 and ARHGEF7. CYK4 GAP mutant cells show cytokinesis defects that are rescued by depletion of ARHGEF7 and PAK1. CYK4 GAP mutant cells; Rac1 activity assay; siRNA depletion of PAK1 and ARHGEF7; immunofluorescence for cytokinesis and adhesion markers The Journal of Cell Biology High 22945935
2005 PAK1 regulates non-muscle myosin II-B heavy chain phosphorylation and filament disassembly in response to EGF. A dominant-negative PAK1 mutant inhibits EGF-dependent myosin II-B heavy chain phosphorylation and filament disassembly and increases myosin light chain phosphorylation, resulting in diminished chemotaxis toward EGF. Dominant-negative PAK1 expression; immunoblot for myosin heavy chain and light chain phosphorylation; myosin IIB localization by immunofluorescence; EGF chemotaxis assay Cellular Signalling Medium 15993754
2006 CXCL1-induced chemotaxis requires activation of Cdc42 and PAK1 downstream of CXCR2. Dominant-negative ERK or MEK inhibitor PD98059 does not block CXCL1-induced PAK1 activation or chemotaxis, placing PAK1 independently of the ERK pathway in this context. PAK1 activity assay after CXCL1 stimulation in CXCR2-expressing HEK293 cells; dominant-negative ERK expression; MEK inhibitor PD98059; Cdc42 activity assay; chemotaxis assay Biochemistry Medium 12033944
2006 CXCL12 and C5a stimulate cell migration via a PAK1/2–p38α MAPK–MAPKAP-K2–HSP27 pathway. PAK1 and PAK2 are required for p38α activation in response to CXCL12. MAPKAP-K2 siRNA blocks CXCL12-induced migration; macrophages lacking MAPKAP-K2 fail to migrate toward C5a; HSP27 siRNA blocks CXCL12-induced migration. RNAi against PAK1, PAK2, MAPKAP-K2, HSP27; p38α kinase-dead and knockout macrophages; p38 inhibitors SB203580 and BIRB0796; migration assays Cellular Signalling High 16574378
2007 PAK1 regulates dendritic branching and spine formation in neurons. Constitutively active PAK1 increases primary branching on apical dendrites and number of basal dendrites in cortical neurons; dominant-negative PAK1 reduces these features. PAK1 also regulates spine morphology in hippocampal neurons. Overexpression of constitutively active and dominant-negative PAK1 in immature cortical and hippocampal neurons; morphometric analysis of dendritic branching and spine number/morphology Developmental Neurobiology Medium 17443815
2015 PAK1 promotes invadopodia turnover by phosphorylating cortactin, facilitating invadopodia disassembly. p27Kip1 promotes PAK1–cortactin interaction; in the absence of p27, PAK1–cortactin interaction is impaired, leading to increased invadopodia stability but reduced invasion capacity. Cortactin mutants at PAK1-targeted phosphorylation sites abolish p27's effect on invadopodia dynamics. Co-immunoprecipitation of p27-cortactin-PAK1; phospho-cortactin mutants for PAK1 sites; siRNA; invadopodia formation and turnover assays; invasion assays eLife High 28287395
2015 PAK1 mediates MORC2 phosphorylation at Ser677. Phospho-mimetic MORC2-S677E enhances cell proliferation and tumorigenicity of gastric cancer cells, whereas phospho-dead MORC2-S677A reduces proliferation, establishing MORC2 as a functional PAK1 substrate in tumorigenesis. In vitro PAK1 kinase assay on MORC2; phospho-mimetic (S677E) and phospho-dead (S677A) MORC2 mutants; cell proliferation and xenograft tumor assays Oncotarget Medium 25888627
2016 GIT1 and βPIX form complexes with PAK1 at centrosomes. GIT1 and PAK1 are positive regulators of microtubule nucleation; βPIX is a negative regulator. PAK1 kinase activity is required for centrosomal microtubule nucleation. GIT1 and βPIX (but not γ-tubulin) are direct substrates for PAK1 in vitro. βPIX directly interacts with γ-tubulin via its C-terminal domain. Co-immunoprecipitation; immunofluorescence at centrosomes; microtubule regrowth assay after siRNA depletion of GIT1, βPIX, or PAK1; phenotypic rescue; in vitro PAK1 kinase assay on GIT1/βPIX/γ-tubulin; pull-down of γ-tubulin binding domains Biochimica et Biophysica Acta High 27012601
2018 De novo PAK1 gain-of-function mutations (Y131C, Y429C) cause reduced homodimerization and enhanced PAK1 kinase activity, resulting in increased phosphorylation of JNK, AKT, and c-JUN, and a cell-spreading phenotype with filopodia enrichment. PAK1 inhibitor FRAX486 reverses the filopodia phenotype. Co-immunoprecipitation and size-exclusion chromatography for dimerization; PAK1 kinase activity assay in patient fibroblasts; phospho-immunoblot for JNK, AKT, c-JUN; cell spreading assay with PAK1 inhibitor American Journal of Human Genetics High 30290153
2018 PAK1 and aPKC act as a dual-kinase mechanism downstream of Cdc42 to specify apical domain identity in epithelia. PAK1 and aPKC phosphorylate overlapping polarity substrates in kinase assays; inactivating both leads to complete loss of epithelial polarity (loss of Crumbs, Par3/Bazooka, ZO-1), whereas loss of either alone has milder effects. Drosophila genetics; mammalian cell transfection; in vitro kinase assays on polarity substrates; immunofluorescence for apical markers in PAK1/aPKC double-inactivation Cell Reports High 29444419
2018 In fission yeast, Pak1 phosphorylates the anillin-like protein Mid1 at its N-terminus to promote Mid1 association with cortical nodes that act as contractile actomyosin ring (CAR) precursors, thereby controlling the spatial placement of the cell division plane. Phosphoproteomic screen for Pak1 substrates; in vitro Pak1 kinase assay on Mid1; phospho-site mutants; GFP-Mid1 localization; genetic rescue by synthetic tethering of Mid1 to cortical nodes The Journal of Cell Biology High 32421151
2020 PAK1-mediated cytoskeleton rearrangement is required for clathrin-mediated endocytosis of the ACE2-SARS-CoV-2 spike complex, which is then degraded via autophagy. Pan-PAK inhibitor FRAX-486 restores ACE2 surface expression, suppresses infection by multiple SARS-CoV-2 strains in vitro, and reduces lung viral load and inflammation in Syrian hamsters. Co-localization and endocytosis assays; FRAX-486 pharmacological inhibition; PAK1 siRNA; ACE2 surface expression by flow cytometry; in vivo hamster model Signal Transduction and Targeted Therapy Medium 37806990
2020 PAK1 associates with filamin A (FLNA) via reciprocal immunoprecipitation and is required for vimentin phosphorylation on Ser39, 56, and 72 following fibronectin binding. PAK1 loss (siRNA or enzyme inhibition) reduces vimentin filament assembly and cell extension formation. FLNA knockdown decreases vimentin phosphorylation at Ser56 and Ser72 and reduces cell extensions. Reciprocal co-immunoprecipitation; siRNA knockdown of PAK1 and FLNA; immunoblot for vimentin phospho-serine; sedimentation assay for vimentin filament assembly; cell extension length measurements Biochimica et Biophysica Acta – Molecular Cell Research Medium 32389644
2021 PAK1 deficiency in mice causes hair cell (HC) apoptosis and severe hearing loss. PAK1 deficiency downregulates cofilin phosphorylation, ezrin-radixin-moesin phosphorylation, and βII-spectrin expression, leading to disorganized HC stereocilia and decreased HC synapse density in the cochlea. Pak1-/- knockout mice; auditory brainstem response; immunofluorescence and scanning electron microscopy of stereocilia; Western blot for p-cofilin, p-ERM, βII-spectrin; synapse quantification Journal of Genetics and Genomics High 34049799
2021 PAK1 positively regulates oligodendrocyte morphologic complexity and myelin internode length. PAK1 inhibition decreases F-actin spreading at oligodendrocyte progenitor cell process tips. Constitutively active AKT in oligodendrocytes (which causes excessive myelin wrapping) increases PAK1 expression. Constitutively active PAK1 in zebrafish increases myelin internode length; PAK1 inhibition decreases internode length. In vitro PAK1 inhibition in oligodendrocyte cultures; constitutively active PAK1 in zebrafish in vivo; F-actin imaging; constitutively active AKT transgenic mice; myelin internode length measurement The Journal of Neuroscience Medium 33478987
2022 PAK1 in skeletal muscle is required for insulin-stimulated GLUT4 vesicle translocation and whole-body glucose homeostasis. Skeletal muscle-specific PAK1 knockout (skmPAK1-iKO) causes glucose intolerance, and PAK1 enrichment preserves GLUT4 translocation under insulin-resistant conditions. PAK1-enriched myotubes secrete a circulating factor that enhances β-cell function (tissue crosstalk). Inducible muscle-specific PAK1 KO and OE mouse models; glucose tolerance and insulin tolerance tests; GLUT4-myc translocation assay; conditioned media experiment on β-cells Frontiers in Endocrinology High 35222279
2013 PAK1 depletion in pancreatic β-cells increases ubiquitination and proteasomal degradation of Survivin protein without changes in Survivin mRNA. Exogenous PAK1 expression prevents hyperglycemia-induced Survivin loss. Overexpression of Survivin restores β-cell proliferation impaired by PAK1 loss. PAK1-/- mouse islets; siRNA knockdown in MIN6 β-cells; ubiquitination assay; immunoblot for Survivin protein and mRNA; rescue with exogenous PAK1; proliferation assay with Survivin overexpression Islets Medium 23514967
2015 PAK1 regulates cortical development by promoting neural progenitor cell proliferation and facilitating neuronal migration. PAK1 knockout mice show reduced pyramidal neurons in multiple cortical layers, a smaller progenitor pool, and impaired neuronal migration. PAK1 knockout mice; cortical layer marker immunohistochemistry; progenitor cell counting; in utero electroporation for neuronal migration analysis Molecular Brain Medium 26043730
2021 Activated PAK1 suppresses NOX2-dependent ROS production and NCX (sodium-calcium exchanger) activity in atrial myocytes, preventing AngII-induced Ca2+ overload and arrhythmic events. PAK1-/- atrial myocytes show enhanced NOX2 activation and arrhythmia susceptibility. PAK1-/- mice; in vivo arrhythmia inducibility testing; ROS measurement; NOX2 inhibitors; NCX inhibitors; intracellular Ca2+ imaging; canine AF model Heart Rhythm High 29625277
2021 PAK1 overexpression in intestinal epithelial cells directly interacts with NF-κB p65 (co-immunoprecipitation), promoting nuclear translocation and increased NF-κB transactivation in a kinase-dependent manner. PAK1 overexpression suppresses PPARγ, which normally inhibits NF-κB; mesalamine recovers PPARγ through PAK1 inhibition. Co-immunoprecipitation of PAK1-p65; PAK1 overexpression and kinase-dead mutant; NF-κB reporter; PAK1-KO small intestinal organoids + TNFα; PPARγ immunoblot Biochimica et Biophysica Acta Medium 26036343
2021 PAK1 directly interacts with Notch1 in colon epithelial cells (co-localization and co-immunoprecipitation). PAK1 silencing leads to Notch1 activation, causing crypt hyperproliferation and impaired goblet cell differentiation in a PAK1/IL10 double-knockout mouse model. Co-immunoprecipitation and immunofluorescence colocalization of PAK1-Notch1; PAK1 silencing experiments; IL10/PAK1 double-KO mice; histological analysis of crypt phenotype Cellular and Molecular Gastroenterology and Hepatology Medium 33189893
2021 Fibrinogen activates PAK1 (phosphorylation) via syndecan-1 signaling. Active PAK1 promotes cofilin dephosphorylation (activation), leading to actin stress fiber disassembly and reduced endothelial permeability. PAK1 siRNA silencing prevents fibrinogen-induced cofilin dephosphorylation and barrier protection. Western blot for pPAK1 and p-cofilin; siRNA knockdown of PAK1; FITC-dextran permeability assay; in vivo hemorrhagic shock mouse model with fibrinogen resuscitation Shock Medium 32433215
2023 PAK1-dependent mechanotransduction mediates myofibroblast nuclear adaptation during fibrosis. Progressive mechanical stress from scarring induces nuclear softening, loss of H3K9Me3, and permissive chromatin accessibility changes that drive profibrotic gene regulation. Genetic loss of PAK1 signaling impairs this mechanoadaptive response in vitro and reduces fibrosis in liver and lung models in vivo. Chromatin accessibility profiling (ATAC-seq); RNA-seq; H3K9Me3 immunofluorescence; PAK1 genetic manipulation in liver and lung fibrosis models; nuclear stiffness measurements Cell Reports Medium 37967011

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Current biology : CB 611 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 274 8824201
1996 The adaptor protein Nck links receptor tyrosine kinases with the serine-threonine kinase Pak1. The Journal of biological chemistry 241 8798379
2002 Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Molecular cell 193 11804587
2000 p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). The Journal of biological chemistry 192 10995762
1997 Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts. Molecular and cellular biology 184 9234703
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 174 21482786
2006 Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients. Journal of the National Cancer Institute 164 16705121
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 136 24859002
2003 Yeast Pak1 kinase associates with and activates Snf1. Molecular and cellular biology 125 12748292
2011 Inhibition or ablation of p21-activated kinase (PAK1) disrupts glucose homeostatic mechanisms in vivo. The Journal of biological chemistry 117 21969371
2010 PAK1 as a therapeutic target. Expert opinion on therapeutic targets 111 20507214
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 108 14670848
2001 Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. The Journal of biological chemistry 107 11733498
2021 DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. The Journal of clinical investigation 106 33945512
2006 CXCL12 and C5a trigger cell migration via a PAK1/2-p38alpha MAPK-MAPKAP-K2-HSP27 pathway. Cellular signalling 103 16574378
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
2003 Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells. FEBS letters 87 12560069
2013 HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Molecular cell 86 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 80 20395366
2017 Targeting PAK1. Biochemical Society transactions 74 28202661
2004 Pak1 protein kinase regulates activation and nuclear localization of Snf1-Gal83 protein kinase. Molecular and cellular biology 74 15340085
2008 PAK1-mediated activation of ERK1/2 regulates lamellipodial dynamics. Journal of cell science 71 18940914
2020 PAK1-blockers: Potential Therapeutics against COVID-19. Medicine in drug discovery 70 32313880
2013 Pak1 kinase links ErbB2 to β-catenin in transformation of breast epithelial cells. Cancer research 66 23576562
2003 Pak1 and PIX regulate contact inhibition during epithelial wound healing. The EMBO journal 64 12912914
2015 Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 63 25595279
2018 Activating Mutations in PAK1, Encoding p21-Activated Kinase 1, Cause a Neurodevelopmental Disorder. American journal of human genetics 62 30290153
2015 miR-30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy. Cardiovascular therapeutics 58 25781190
2007 Pak1 regulates dendritic branching and spine formation. Developmental neurobiology 58 17443815
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
2013 Herbal therapeutics that block the oncogenic kinase PAK1: a practical approach towards PAK1-dependent diseases and longevity. Phytotherapy research : PTR 53 23943274
2012 DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, inhibiting cell migration and invasion. Oncology reports 53 23233092
2015 Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer. Inflammatory bowel diseases 51 25569743
2020 Desmoglein-2 modulates tumor progression and osimertinib drug resistance through the EGFR/Src/PAK1 pathway in lung adenocarcinoma. Cancer letters 48 32272148
2014 PAK1 mediates pancreatic cancer cell migration and resistance to MET inhibition. The Journal of pathology 47 25074413
2015 PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion. Cell death & disease 46 25766321
2013 PAK1 mediates resistance to PI3K inhibition in lymphomas. Clinical cancer research : an official journal of the American Association for Cancer Research 45 23300274
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
2007 JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions. The Journal of biological chemistry 45 17726028
2023 Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK. Biophysical reviews 44 37124926
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
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 41 27117533
2015 PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation. Biochimica et biophysica acta 41 26036343
2018 Protein Kinase C-ζ stimulates colorectal cancer cell carcinogenesis via PKC-ζ/Rac1/Pak1/β-Catenin signaling cascade. Biochimica et biophysica acta. Molecular cell research 39 29408512
2017 The p21-activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration. British journal of pharmacology 39 28574147
2016 PAK1-cofilin phosphorylation mediates human lung adenocarcinoma cells migration induced by apelin-13. Clinical and experimental pharmacology & physiology 39 26918678
2015 PAK1-mediated MORC2 phosphorylation promotes gastric tumorigenesis. Oncotarget 39 25888627
2009 Dissecting activation of the PAK1 kinase at protrusions in living cells. The Journal of biological chemistry 38 19574218
2016 microRNA-7 regulates cell growth, migration and invasion via direct targeting of PAK1 in thyroid cancer. Molecular medicine reports 37 27430434
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 36 24347489
2005 PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis. Cellular signalling 36 15993754
2009 PAK1 and PAK2 have different roles in HGF-induced morphological responses. Cellular signalling 35 19628037
2002 PAK1 kinase is required for CXCL1-induced chemotaxis. Biochemistry 34 12033944
2021 Disruption of the autism-related gene Pak1 causes stereocilia disorganization, hair cell loss, and deafness in mice. Journal of genetics and genomics = Yi chuan xue bao 32 34049799
2013 Expression and significance of Rac1, Pak1 and Rock1 in gastric carcinoma. Asia-Pacific journal of clinical oncology 32 23298303
2020 circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis. Cancer gene therapy 31 32855541
2005 Spatiotemporal regulation of the Pak1 kinase. Biochemical Society transactions 31 16042564
2021 PAK1 Positively Regulates Oligodendrocyte Morphology and Myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 33478987
2019 Identification of a novel PAK1 inhibitor to treat pancreatic cancer. Acta pharmaceutica Sinica. B 30 32322465
2015 PAK1 regulates cortical development via promoting neuronal migration and progenitor cell proliferation. Molecular brain 30 26043730
2018 Pak1 Kinase Maintains Apical Membrane Identity in Epithelia. Cell reports 29 29444419
2017 Engineering Pak1 Allosteric Switches. ACS synthetic biology 29 28365983
2021 p21-Activated kinase 1 (PAK1) in aging and longevity: An overview. Ageing research reviews 25 34390849
2020 Fission yeast Pak1 phosphorylates anillin-like Mid1 for spatial control of cytokinesis. The Journal of cell biology 25 32421151
2019 Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma. Cell communication and signaling : CCS 25 31660987
2018 Loss of p21-activated kinase 1 (Pak1) promotes atrial arrhythmic activity. Heart rhythm 25 29625277
2016 GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation. Biochimica et biophysica acta 25 27012601
2010 Cadherins and Pak1 control contact inhibition of proliferation by Pak1-betaPIX-GIT complex-dependent regulation of cell-matrix signaling. Molecular and cellular biology 24 20154149
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 23 38785043
2023 The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation. Cell death & disease 22 37225681
2022 Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis. Frontiers in endocrinology 22 35222279
2020 Cooperative roles of PAK1 and filamin A in regulation of vimentin assembly and cell extension formation. Biochimica et biophysica acta. Molecular cell research 22 32389644
2019 Effect of P21-activated kinase 1 (PAK-1) inhibition on cancer cell growth, migration, and invasion. Pharmacology research & perspectives 21 31516713
2018 PAK1 overexpression promotes cell proliferation in cutaneous T cell lymphoma via suppression of PUMA and p21. Journal of dermatological science 21 29307600
2023 PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis. Cell reports 20 37967011
2022 Development and Utility of a PAK1-Selective Degrader. Journal of medicinal chemistry 20 36416208
2021 Fibrinogen Activates PAK1/Cofilin Signaling Pathway to Protect Endothelial Barrier Integrity. Shock (Augusta, Ga.) 19 32433215
2020 Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma. Journal of cellular and molecular medicine 19 32237037
2019 PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions. Scientific reports 19 31748572
2014 PAK1 is a novel cardiac protective signaling molecule. Frontiers of medicine 19 25416031
2021 PAK1 and PAK2 in cell metabolism regulation. Journal of cellular biochemistry 18 34750857
2023 PAK1 and Therapy Resistance in Melanoma. Cells 17 37830586
2013 Depletion of PAK1 enhances ubiquitin-mediated survivin degradation in pancreatic β-cells. Islets 17 23514967
2020 Current trends and opportunities in targeting p21 activated kinase-1(PAK1) for therapeutic management of breast cancers. Gene 16 32717309
2020 A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation. Cellular and molecular gastroenterology and hepatology 16 33189893
2024 CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression. Cancer letters 15 38364963
2023 P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-CoV-2 entry and ACE2 autophagic degradation. Signal transduction and targeted therapy 15 37806990
2015 PAK1 promotes intestinal tumor initiation. Cancer prevention research (Philadelphia, Pa.) 15 26304465

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