Affinage

PAK4

Serine/threonine-protein kinase PAK 4 · UniProt O96013

Length
591 aa
Mass
64.1 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

PAK4 is a Cdc42-activated serine/threonine kinase that functions as a central integrator of cytoskeletal remodeling, cell survival, cell polarity, and transcriptional regulation downstream of Rho-family GTPases. Upon binding GTP-loaded Cdc42, PAK4 autophosphorylates at Ser474 to become catalytically active and phosphorylates diverse substrates including LIMK1 and N-WASP (driving Arp2/3-dependent actin polymerization), paxillin (regulating focal adhesion turnover), β-catenin at Ser675 (promoting Wnt/TCF/LEF transcription), Bad (inhibiting apoptosis), CRTC1 at Ser215 (activating CREB-dependent neuroprotective gene expression), and Smad2 (triggering its degradation to antagonize TGF-β signaling) (PMID:9822598, PMID:11668177, PMID:18424072, PMID:20406887, PMID:22173096, PMID:27903866, PMID:23934187, PMID:29100370). PAK4 also operates through kinase-independent scaffolding, notably stabilizing RhoU by shielding it from Rab40A-Cullin5-mediated ubiquitination and antagonizing caspase-8 activation at death receptors (PMID:26598620, PMID:14560027). Its activity is modulated by SETD6-mediated lysine methylation at K473, which enhances β-catenin interaction and Wnt target gene transcription while reducing focal adhesion integrity, and by CDK15-mediated phosphorylation at Ser291, which promotes β-catenin/c-Myc and MEK/ERK signaling (PMID:26841865, PMID:33051544, PMID:34262144). PAK4 knockout in mice causes embryonic lethality with cardiac and neural developmental defects, and conditional neural deletion impairs progenitor proliferation and adherens junction formation, establishing PAK4 as essential for vertebrate development (PMID:14517283, PMID:21382368).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    The identification of PAK4 as a novel Cdc42 effector that localizes to the Golgi and induces filopodia established that a distinct group II PAK kinase links Rho-family GTPase signaling to actin cytoskeletal remodeling.

    Evidence Co-immunoprecipitation of PAK4 with GTP-bound Cdc42, immunofluorescence showing Golgi relocalization and filopodia induction in transfected cells

    PMID:9822598

    Open questions at the time
    • Endogenous substrates mediating actin remodeling were unknown
    • Physiological activation context beyond overexpression was undefined
  2. 2001 High

    Mapping the Ser474 autophosphorylation site as the activating event, and demonstrating that constitutively active PAK4 transforms fibroblasts while kinase-dead PAK4 blocks Ras transformation, established PAK4 as an oncogenic kinase and defined its activation mechanism.

    Evidence Phosphospecific antibody, S474E constitutive activation mutant, soft agar colony formation and focus formation assays

    PMID:11313478 PMID:11668177

    Open questions at the time
    • Upstream signals triggering Ser474 autophosphorylation in vivo were unclear
    • Direct transformation targets were unidentified
  3. 2001 High

    Demonstrating that PAK4 phosphorylates Bad and inhibits caspase activation provided the first direct survival substrate, while a subsequent study showed kinase-independent caspase-8 antagonism, revealing dual mechanisms for anti-apoptotic function.

    Evidence Bad phosphorylation assay, caspase activity assays under TNF-α/UV/serum deprivation, kinase-dead mutant retaining caspase-8 inhibition

    PMID:11278822 PMID:14560027

    Open questions at the time
    • The precise kinase-independent mechanism for caspase-8 inhibition was not structurally resolved
    • Whether Bad phosphorylation is direct in endogenous settings was not confirmed
  4. 2003 High

    PAK4 knockout embryonic lethality with cardiac and neural defects proved that PAK4 is non-redundant with other PAK family members for vertebrate development, particularly for heart and spinal cord morphogenesis.

    Evidence Homologous recombination knockout, histological analysis of E11.5 embryos

    PMID:14517283

    Open questions at the time
    • Which PAK4 substrates mediate the cardiac versus neuronal phenotypes was unknown
    • Conditional tissue-specific requirements had not yet been dissected
  5. 2005 Medium

    Showing that endogenous PAK4 promotes TRADD recruitment to TNF-R1 and activates NF-κB/ERK pathways placed PAK4 as an upstream organizer of TNF receptor signaling complexes, not merely an anti-apoptotic effector.

    Evidence RNAi knockdown of endogenous PAK4, TRADD co-immunoprecipitation with TNF-R, NF-κB and ERK assays

    PMID:16227624

    Open questions at the time
    • Whether PAK4 directly phosphorylates TRADD or a scaffold component was not determined
    • Single-lab finding without independent replication
  6. 2007 High

    Crystal structures of the active PAK4 catalytic domain revealed the structural basis for group II PAK activation, including αC helix rearrangements that distinguish it from group I PAKs, and enabled structure-based inhibitor design.

    Evidence Multiple X-ray crystal structures including inhibitor co-crystal

    PMID:17292838

    Open questions at the time
    • Full-length PAK4 structure with autoinhibitory domain was not resolved
    • How Cdc42 binding allosterically activates the kinase domain was structurally undefined
  7. 2008 High

    Identification of LIMK1 as a direct PAK4 substrate linking HGF signaling to cofilin phosphorylation and cell migration established the PAK4→LIMK1→cofilin pathway as a core actin regulatory axis.

    Evidence In vitro kinase assay, FRET-FLIM co-localization at cell periphery, siRNA and migration assays in prostate cancer cells

    PMID:18424072

    Open questions at the time
    • Specific LIMK1 phosphorylation site(s) by PAK4 were not mapped
    • Whether this pathway operates in non-cancer contexts was untested
  8. 2010 High

    Demonstrating that PAK4 phosphorylates paxillin at Ser272 at focal adhesions and is recruited to cell-cell junctions via Cdc42 for junction maturation expanded PAK4's role from actin dynamics to adhesion-dependent signaling at two distinct subcellular compartments.

    Evidence In vitro kinase assay and immunofluorescence for paxillin; siRNA screen of 36 Cdc42 targets for junction maturation in bronchial epithelial cells

    PMID:20406887 PMID:20631255

    Open questions at the time
    • How PAK4 is differentially targeted to focal adhesions versus junctions was unclear
    • The junctional substrates downstream of PAK4 at cell-cell contacts were unidentified
  9. 2011 High

    Discovery that PAK4 shuttles between nucleus and cytoplasm via CRM1/importin-α5 and phosphorylates nuclear β-catenin at Ser675 to activate TCF/LEF transcription established a direct role for PAK4 in Wnt pathway transcriptional output.

    Evidence Deletion mutant mapping of NLS/NES, nuclear fractionation, ChIP showing PAK4 at TCF/LEF-bound chromatin, β-catenin Ser675 phosphorylation assay

    PMID:22173096

    Open questions at the time
    • Which Wnt ligands activate this nuclear PAK4 pool was unknown
    • Whether nuclear PAK4 kinase activity is regulated differently from cytoplasmic activity was not addressed
  10. 2011 High

    Conditional neural knockout revealed that PAK4 is essential for cortical progenitor proliferation, neurosphere self-renewal, and adherens junction maintenance, connecting its junctional and cytoskeletal functions to brain development.

    Evidence Nestin-Cre conditional knockout, BrdU proliferation assay, neurosphere culture, histological analysis

    PMID:21382368

    Open questions at the time
    • Downstream substrates responsible for neural progenitor proliferation were not identified
    • Whether cardiac-specific conditional knockout phenocopies the global knockout heart defect was only partially addressed
  11. 2013 High

    Identification of Smad2/3 as PAK4 substrates and interactors, with PAK4 phosphorylation triggering Smad2 ubiquitin-dependent degradation, revealed a mechanism by which HGF/PAK4 antagonizes TGF-β tumor-suppressive signaling.

    Evidence Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay with kinase-dead controls

    PMID:23934187

    Open questions at the time
    • The E3 ligase mediating Smad2 degradation downstream of PAK4 was not identified
    • In vivo relevance in tumor models was not tested
  12. 2015 High

    Demonstrating that PAK4 stabilizes RhoU by preventing Rab40A-Cullin5-mediated ubiquitination, and that RhoU rescues PAK4 depletion adhesion phenotypes, established a kinase-independent scaffolding function distinct from PAK4's catalytic roles.

    Evidence Ubiquitination assay, RhoU rescue of PAK4-depleted cells, co-immunoprecipitation

    PMID:26598620

    Open questions at the time
    • Structural basis for how PAK4 shields RhoU from the E3 ligase was unknown
    • Whether other substrates of Rab40A-Cullin5 are similarly protected was not investigated
  13. 2016 High

    SETD6-mediated methylation of PAK4 at K473 was shown to enhance β-catenin binding and Wnt target transcription, establishing lysine methylation as a post-translational regulatory layer on PAK4 that modulates its transcriptional functions and adhesion properties.

    Evidence In vitro methylation assay, ChIP for PAK4/β-catenin at Wnt target promoters, focal adhesion and migration assays with K473 mutants

    PMID:26841865 PMID:33051544

    Open questions at the time
    • Conditions under which SETD6 methylates PAK4 physiologically were not defined
    • Whether demethylases reverse this modification was unknown
  14. 2016 High

    Identification of CRTC1-Ser215 as a PAK4 substrate that activates CREB-dependent expression of Bcl-2, BDNF, and PGC-1α in dopaminergic neurons defined a PAK4→CRTC1→CREB neuroprotective signaling axis with therapeutic implications for neurodegeneration.

    Evidence Site-directed mutagenesis of CRTC1 S215, viral delivery of constitutively active PAK4 in rat Parkinson's disease models, Western blot for CREB targets

    PMID:27903866

    Open questions at the time
    • Endogenous upstream activators of PAK4 in neurons were not defined
    • Long-term neuroprotective efficacy was not assessed
  15. 2017 High

    N-WASP phosphorylation at Ser484/485 by PAK4, promoting Arp2/3-dependent actin polymerization in vitro, and a systematic PAK4 interactome enriched in actin regulators, proteasome, and replication fork components, broadened the substrate repertoire and pointed to additional PAK4 functions.

    Evidence In vitro kinase assay, reconstituted actin polymerization assay, iTRAQ quantitative mass spectrometry of PAK4 immunoprecipitates

    PMID:29100370

    Open questions at the time
    • Many interactome hits (replication fork, CCT) were not functionally validated
    • In vivo relevance of N-WASP Ser484/485 phosphorylation was not tested
  16. 2018 High

    The crystal structure of full-length PAK4 in complex with CDC42 revealed additional contacts beyond the CRIB domain — involving the kinase C-lobe and polybasic region — explaining higher affinity of full-length PAK4 for Cdc42 and resolving how GTPase binding modulates kinase activity.

    Evidence X-ray crystallography, SAXS, binding affinity measurements, kinase assays

    PMID:29295922

    Open questions at the time
    • How the autoinhibitory domain is released upon Cdc42 binding at a conformational dynamics level was not captured
    • Structures with downstream substrates bound were not obtained
  17. 2019 High

    PAK4 phosphorylation of fumarase at Ser46 sequesters it in the cytoplasm via 14-3-3 binding, preventing nuclear FH/CSL/p53-driven p21 transcription, revealing a mechanism by which PAK4 overrides metabolic tumor-suppressive checkpoints.

    Evidence In vitro kinase assay, S46A mutagenesis, 14-3-3 co-immunoprecipitation, ChIP for nuclear FH complex

    PMID:30683654

    Open questions at the time
    • Whether this mechanism operates in normal non-cancer physiology was not tested
    • The quantitative contribution of FH phosphorylation to overall PAK4 oncogenicity was not established
  18. 2020 High

    Demonstrating that PAK4 reprograms tumor endothelial cells via MEF2D/ZEB1/SLUG-mediated downregulation of claudin-14 and VCAM-1, impairing T cell adhesion and infiltration, established PAK4 as a cell-non-autonomous regulator of anti-tumor immunity.

    Evidence PAK4 knockout in endothelial cells, transcriptome analysis, ChIP for MEF2D/ZEB1/SLUG at target promoters, T cell adhesion assay, in vivo glioblastoma models

    PMID:35121889

    Open questions at the time
    • Whether PAK4 directly phosphorylates MEF2D or acts indirectly was not resolved
    • Relevance to non-brain tumor vasculature was not tested
  19. 2021 High

    CDK15 was identified as an upstream kinase phosphorylating PAK4 at Ser291 to drive β-catenin/c-Myc and MEK/ERK signaling in colorectal cancer, and BioID proximity proteomics placed PAK4 specifically at the Afadin/nectin junctional sub-compartment with 17 junctional phosphosubstrates.

    Evidence CDK15 in vitro kinase assay with S291 mutagenesis, AOM/DSS mouse model, PDX model; BioID proximity labeling, quantitative phosphoproteomics with PAK4 inhibitors

    PMID:34262144 PMID:34493720

    Open questions at the time
    • How CDK15-mediated Ser291 phosphorylation changes PAK4 structure or substrate selectivity was unknown
    • Functional validation of the 17 junctional phosphosites was incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanisms by which PAK4 selectively partitions between its junctional, focal adhesion, nuclear, and Golgi pools, and how post-translational modifications (K473 methylation, S291 phosphorylation, S474 autophosphorylation) coordinately tune substrate selectivity in each compartment, remain unresolved.
  • No integrated model of compartment-specific PAK4 regulation exists
  • In vivo substrate phosphoproteomics across tissues is lacking
  • Whether PAK4's kinase-independent scaffolding functions extend beyond RhoU stabilization and caspase-8 inhibition is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 14 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1
Partners
AFDNCDC42CTNNB1LIMK1PXNRHOUSETD6WASL
Complex memberships
Afadin/nectin junctional complexPar6B/aPKC polarity complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PAK4 was identified as a novel effector for Cdc42Hs, interacting only with the activated (GTP-bound) form through its GTPase-binding domain (GBD). Co-expression with constitutively active Cdc42HsV12 redistributes PAK4 to the Golgi membrane and induces filopodia and actin polymerization in a kinase activity-dependent manner. Co-expression, co-immunoprecipitation, dominant-negative/active mutants, immunofluorescence localization The EMBO journal High 9822598
2001 Serine 474 in the PAK4 kinase domain was identified as an autophosphorylation site in vivo; the S474E mutation confers constitutive kinase activation, and activated PAK4 (S474E) transforms NIH3T3 cells for anchorage-independent growth, while kinase-inactive PAK4 (K350A/K351A) blocks Ras-driven transformation. Phosphospecific antibody generation, site-directed mutagenesis, soft agar colony assay, co-expression with activated Cdc42 The Journal of biological chemistry High 11668177
2001 PAK4 protects cells from apoptosis by phosphorylating the proapoptotic protein Bad, leading to inhibition of caspase activation. Expression of wild-type or constitutively active PAK4 delays apoptosis induced by TNF-α, UV irradiation, and serum starvation. Overexpression of wild-type and constitutively active PAK4 mutants, phosphorylation assay of Bad, caspase activation assay The Journal of biological chemistry High 11278822
2001 Constitutively active PAK4 dissolves actin stress fibers and focal adhesions, impairs cell spreading on fibronectin, and induces anchorage-independent growth in fibroblasts. Dominant-negative PAK4 inhibits Dbl-induced focus formation, placing PAK4 downstream of Rho GTPase exchange factors in oncogenic transformation. Expression of activated/dominant-negative PAK4 mutants, soft agar assay, focus formation assay, immunofluorescence Molecular and cellular biology High 11313478
2003 PAK4 knockout in mice causes embryonic lethality by E11.5 with defects in fetal heart development and spinal cord motor neuron/interneuron differentiation and migration, establishing PAK4 as essential for neuronal development and cytoskeletal organization in vivo. Gene knockout (homologous recombination), histological analysis, phenotypic characterization of PAK4-null embryos Molecular and cellular biology High 14517283
2003 PAK4 inhibits death receptor-induced apoptosis by antagonizing initiator caspase 8 activation, independent of PAK4 kinase activity, potentially by blocking caspase 8 recruitment to death domain receptors (TNF-R, Fas). Overexpression of kinase-active and kinase-dead PAK4, caspase 8 activity assay, apoptosis assay with TNF-α/Fas stimulation Molecular and cellular biology Medium 14560027
2005 Endogenous PAK4 is required for optimal TRADD binding to the activated TNF-α receptor through both kinase-dependent and kinase-independent mechanisms, thereby enabling full activation of NF-κB and ERK pro-survival pathways downstream of TNF-α. RNAi knockdown of endogenous PAK4, co-immunoprecipitation of TRADD with TNF-R, NF-κB and ERK pathway assays The Journal of biological chemistry Medium 16227624
2006 PAK4 and alphaPIX regulate podosome size and number in primary human macrophages; kinase-active PAK4 increases podosome size while kinase-inactive PAK4 decreases it, demonstrating kinase activity-dependent regulation of localized actin dynamics at podosomes. Immunofluorescence, shRNA knockdown, transfection of kinase-active/-inactive PAK4 mutants, microarray Journal of cellular physiology Medium 16897755
2007 Crystal structures of active, monophosphorylated PAK4 catalytic domain (along with PAK5 and PAK6) revealed domain plasticity including rearrangements of helix αC with an additional helical turn, forming interactions that link the glycine-rich loop, αC, and the activation segment to anchor αC in an active conformation. A tri-substituted purine inhibitor was co-crystallized with PAK4. X-ray crystallography (multiple high-resolution structures), inhibitor co-crystallization Structure High 17292838
2008 PAK4 binds to and phosphorylates LIMK1 in an HGF-dependent manner in prostate cancer cells, altering cofilin phosphorylation levels, cell morphology, and migration speed. PAK4 and LIMK1 interact in small foci at the cell periphery as confirmed by FRET-FLIM. Co-immunoprecipitation, in vitro kinase assay, FRET-FLIM, siRNA knockdown, cell migration assay Cellular signalling High 18424072
2008 The PAK4-JNK signaling pathway acts as a negative regulator of Streptococcus pneumoniae pneumolysin-induced MUC5AC mucin transcription; MKP1 inhibits this PAK4-JNK pathway (induced via TLR4-MyD88-TRAF6-ERK) to upregulate MUC5AC production. Signaling pathway inhibitor studies, mucosal epithelial cell assays, MUC5AC transcription reporter assay The Journal of biological chemistry Medium 18782768
2010 PAK4 localizes at focal adhesions, co-immunoprecipitates with paxillin, and directly phosphorylates paxillin on serine 272, regulating focal adhesion turnover and cell migration in prostate cancer cells. PAK4 also regulates RhoA activity via GEF-H1. Co-immunoprecipitation, in vitro kinase assay, immunofluorescence localization, siRNA knockdown, cell migration assay Journal of cell science High 20406887
2010 Cdc42-dependent recruitment of PAK4 to nascent cell-cell contacts is required for the maturation of primordial junctions into apical junctions in human bronchial epithelial cells; PAK4 kinase activity is essential for junction maturation, and Par6B/aPKC retains PAK4 at junction sites. siRNA library screen of 36 Cdc42 targets, immunofluorescence, dominant-active PAK4 overexpression Molecular biology of the cell High 20631255
2011 CDK5RAP3 is a novel binding partner of PAK4 that enhances PAK4 kinase activity; PAK4 knockdown in CDK5RAP3-overexpressing HCC cells reverses CDK5RAP3-mediated enhanced invasiveness, placing PAK4 as an essential downstream effector of CDK5RAP3. Co-immunoprecipitation, siRNA knockdown, in vitro kinase assay, invasion assay Cancer research Medium 21385901
2011 PAK4 is a nucleo-cytoplasmic shuttling protein containing three nuclear export signals (NESs) and two nuclear localization signals (NLSs); it is exported via CRM-1-dependent pathway and imported via importin α5. Nuclear PAK4 phosphorylates β-catenin on Ser675, stabilizes β-catenin, promotes TCF/LEF transcriptional activity, and associates with the TCF/LEF transcriptional complex at chromatin. Deletion mutant analysis, nuclear/cytoplasmic fractionation, co-immunoprecipitation, phosphorylation assay, ChIP, luciferase reporter assay Biochimica et biophysica acta High 22173096
2011 Conditional nervous system-specific knockout of Pak4 (nestin-Cre) causes reduced proliferation and self-renewal of cortical and striatal neural progenitor cells, cortical thinning, impaired neurogenesis, and loss of neuroepithelial adherens junctions, establishing PAK4 as essential for neural progenitor cell proliferation and brain development. Conditional knockout (Cre-lox), BrdU proliferation assay, neurosphere culture, histological analysis Developmental biology High 21382368
2011 Conditional deletion of PAK4 in secondary heart field progenitors causes abnormal outflow tract development and cardiomyocytes depleted of PAK4 show reduced LIMK1 levels and severely compromised sarcomeric structure, placing PAK4 upstream of LIMK1 in cardiac cytoskeletal organization. Conditional knockout, histological/echocardiographic analysis, PAK4 knockdown in cultured cardiomyocytes, LIMK1 western blot Transgenic research Medium 22173944
2012 PAK4 directly interacts with MMP-2 through its kinase domain (demonstrated by GST pull-down), and PAK4 regulates αvβ3-integrin and phospho-EGFR survival signaling in glioma cells; dual PAK4/MMP-2 depletion causes robust anoikis-mediated cell death. GST pull-down, siRNA knockdown, anoikis assay, cDNA-PCR arrays Cell death & disease Medium 23254288
2012 PAK4 depletion results in defective astral microtubule networks, failure of spindle centering, and prolonged metaphase-like state with chromosome scattering; PAK4 regulates dynein/dynactin complex localization at kinetochores and on astral microtubules, establishing PAK4 as required for metaphase spindle positioning and anchoring. siRNA knockdown, live cell imaging, immunofluorescence, spindle orientation analysis Oncogene Medium 22450748
2013 PAK4 interacts with Smad2/3 via a kinase-independent mechanism that blocks TGF-β1-induced phosphorylation of Smad2 Ser465/467 and Smad3 Ser423/425. Additionally, PAK4 phosphorylates Smad2 on Ser465, leading to its ubiquitin-proteasome-dependent degradation under HGF stimulation. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, kinase-inactive mutant analysis Oncogene High 23934187
2013 PAK4 kinase phosphorylates SCG10 (stathmin-2) on serine 50, regulating microtubule dynamics to promote gastric cancer cell migration and invasion; inhibition of PAK4 by LCH-7749944 or RNAi blocks Ser50 phosphorylation and cell invasion. In vitro kinase assay, site-directed mutagenesis, phospho-specific antibody, xenograft mouse model, siRNA knockdown Oncogene High 23893240
2013 SH3RF2 binds PAK4 and inhibits its ubiquitin-proteasome-dependent degradation through steric hindrance, stabilizing PAK4 protein levels. Loss of SH3RF2 reduces TRADD recruitment to TNF-R1 and impairs NF-κB signaling, consistent with PAK4 stabilization being required for these downstream effects. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, siRNA knockdown Carcinogenesis Medium 24130170
2014 NDRG1 reduces nuclear localization of PAK4, thereby inhibiting PAK4-dependent nuclear translocation of β-catenin and downstream TCF/LEF transcriptional activity; this defines a NDRG1→PAK4→β-catenin nuclear transport axis. Nuclear/cytoplasmic fractionation, Co-immunoprecipitation, reporter assay, immunofluorescence Journal of cell science Medium 24829151
2015 PAK4 phosphorylates Par6B at Ser143, blocking Par6B's interaction with Cdc42, providing a feedback mechanism to control Par6B subcellular localization and polarity complex formation in apical junction assembly. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, immunofluorescence The Biochemical journal Medium 25662318
2015 PAK4 stabilizes RhoU protein in a kinase-independent manner by protecting it from ubiquitination by the Rab40A-Cullin 5 E3 ligase complex; RhoU overexpression rescues the PAK4 depletion adhesion-turnover phenotype, defining a kinase-independent scaffolding function of PAK4. siRNA depletion, ubiquitination assay, RhoU rescue experiment, co-immunoprecipitation, cell adhesion/migration assay The Journal of cell biology High 26598620
2015 In cellulo crystal structure of human PAK4 catalytic domain in complex with its endogenous inhibitor Inka1 was determined at 2.95 Å resolution, revealing how the PAK4 catalytic domain binds cellular ATP and Inka1. The PAK4-PAK4 lattice forms a hexagonal array accommodating other proteins fused to Inka1. In cellulo X-ray crystallography, live-cell crystal imaging with Inka1-GFP Nature communications High 26607847
2015 Integrin αvβ3 recruits and activates PAK4 to counteract senescence in glioblastoma cells; targeting either αvβ3 or PAK4 leads to p21-dependent, p53-independent cell senescence, establishing an αvβ3→PAK4 axis that enables glioblastoma cells to evade oncogene-induced senescence. RNAi knockdown, genetic deletion, senescence assay (SA-β-galactosidase), p21/p53 analysis Cancer research Medium 26297735
2016 SETD6 methyltransferase methylates PAK4 both in vitro and at chromatin in cells; SETD6 methylation of PAK4 dramatically increases the PAK4-β-catenin physical interaction and promotes transcription of Wnt/β-catenin target genes. In vitro methylation assay, co-immunoprecipitation, luciferase reporter assay, ChIP, siRNA depletion of SETD6 The Journal of biological chemistry High 26841865
2016 Drosophila Pak4/Mbt phosphorylates β-catenin/Armadillo to regulate AJ morphogenesis and stability during zonula adherens remodeling; this β-catenin phosphorylation is required for retention of Par3/Bazooka at the remodeling ZA and cooperates with Par1-dependent lateral exclusion to regulate apical membrane differentiation. Conditional genetics, phosphorylation assay, immunofluorescence in Drosophila epithelium, AJ morphogenesis assay Cell reports High 27052178
2016 PAK4 promotes neuroprotection of dopaminergic neurons by phosphorylating CRTC1 (CREB-regulated transcription coactivator) at S215; non-phosphorylatable CRTC1-S215A abolishes the ability of constitutively active PAK4 to induce Bcl-2, BDNF, and PGC-1α expression through CREB, defining a PAK4→CRTC1-S215→CREB neuroprotective axis. Constitutively active PAK4 expression, site-directed mutagenesis of CRTC1, viral delivery in rat PD models, Western blot for CREB targets Science translational medicine High 27903866
2017 PAK4 phosphorylates N-WASP at Ser484/Ser485 and promotes Arp2/3-dependent actin polymerization in vitro; PAK4 ablation reduces N-WASP phosphorylation and alters the G-actin/F-actin balance and actin organization in cells. The PAK4 interactome (by iTRAQ mass spectrometry) is enriched in 14-3-3, proteasome, replication fork, CCT, and Arp2/3 complexes. iTRAQ quantitative MS of PAK4 immunoprecipitations, in vitro kinase assay, in vitro actin polymerization assay, PAK4 ablation Oncotarget High 29100370
2017 PAK4 regulates G6PD activity and cellular pentose phosphate pathway flux by enhancing Mdm2-mediated ubiquitination and degradation of p53, thereby promoting glucose uptake, NADPH production, and lipid biosynthesis in colon cancer cells. Co-immunoprecipitation, ubiquitination assay, G6PD activity assay, metabolic flux analysis, siRNA knockdown Cell death & disease Medium 28542136
2017 PAK4 interacts with the p85α regulatory subunit of PI3K; PAK4-deficient pancreatic cancer cells show reduced Akt phosphorylation downstream of HGF signaling, implicating PAK4 within the PI3K/Akt pathway via p85α. Co-immunoprecipitation, siRNA knockdown, Western blot for p-Akt, HGF-stimulated migration assay Scientific reports Medium 28205613
2017 Zic2 transcription factor directly binds the PAK4 promoter and activates PAK4 transcription (shown by ChIP and luciferase assay); PAK4 mediates Zic2-driven HCC cell growth via the Raf/MEK/ERK pathway. ChIP assay, luciferase reporter assay, siRNA knockdown epistasis, MEK/ERK pathway inhibition Cancer letters Medium 28577975
2018 Crystal structure and solution scattering of full-length PAK4 in complex with CDC42 revealed that beyond the canonical CRIB domain interaction, the PAK4 kinase C-lobe and polybasic region also contact CDC42, increasing binding affinity for full-length PAK4 and modulating kinase activity. X-ray crystallography, small-angle X-ray scattering (SAXS), kinase activity assay, binding affinity measurements Proceedings of the National Academy of Sciences of the United States of America High 29295922
2019 PAK4 phosphorylates CEBPB on Thr-235, which activates CEBPB-mediated transcription of claudin-4 (CLDN4), promoting breast cancer cell migration and invasion in a PAK4-CEBPB-CLDN4 axis. siRNA knockdown, luciferase reporter assay (CLDN4 promoter), Western blot for p-CEBPB, rescue experiments Biochemical and biophysical research communications Medium 30808546
2019 Nuclear PAK4 (nPAK4) co-translocates with ERα from cytoplasm to nucleus upon 17β-estradiol stimulation, represses ERα-mediated transactivation, and promotes bone metastasis of ER+ breast cancer cells by targeting LIFR (a bone metastasis suppressor) through a PAK4-ERα nuclear axis. Nuclear/cytoplasmic fractionation, co-immunoprecipitation, ChIP, luciferase reporter, in vivo metastasis model Oncogene Medium 30177834
2019 PAK4 phosphorylates fumarase (FH) at Ser46, causing FH to bind 14-3-3 protein and become sequestered in the cytosol, thereby preventing formation of the FH/CSL/p53 nuclear complex that drives p21 transcription and TGF-β-induced cell growth arrest in lung cancer cells. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, ChIP, cell growth arrest assay Cancer research High 30683654
2019 PAK4 phosphorylates CRTC1 at S215 to activate CREB signaling and protect motor neurons from degeneration; the PAK4/CREB pathway is inhibited in ALS models and PAK4 overexpression in spinal neurons of hSOD1G93A rats suppresses motor neuron degeneration and prolongs survival. Constitutively active PAK4 overexpression, CREB inhibitor experiments, in vivo spinal injection, rotarod motor function test, apoptosis assay Cell proliferation Medium 33615605
2020 SETD6-mediated methylation of PAK4 at lysine 473 (K473) activates β-catenin transcriptional activity and inhibits cell adhesion by reducing paxillin localization to focal adhesions, decreasing filopodia, actin structures, and cell migration/invasion. Site-directed mutagenesis (K473 methylation site), immunofluorescence of focal adhesions/paxillin, β-catenin reporter assay, cell adhesion assay Scientific reports High 33051544
2020 PAK4 reprograms glioblastoma tumor endothelial cells through a MEF2D/ZEB1- and SLUG-mediated mechanism that downregulates claudin-14 and VCAM-1 expression, enhancing vessel permeability and reducing T cell adhesion to the endothelium; PAK4 knockout in ECs reduces vascular abnormalities and improves T cell infiltration. PAK4 knockout in ECs, transcriptome analysis, ChIP for MEF2D/ZEB1/SLUG at claudin-14 and VCAM-1 promoters, T cell adhesion assay, in vivo tumor models Nature cancer High 35121889
2021 CDK15 binds PAK4 and phosphorylates it at Ser291, promoting colorectal cancer cell proliferation and anchorage-independent growth through β-catenin/c-Myc and MEK/ERK signaling pathways; PAK4 inhibition reverses CDK15-driven tumorigenesis. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (S291), CDK15 knockout in mice (AOM/DSS model), PDX model Cell death and differentiation High 34262144
2021 BioID proximity proteomics revealed that PAK4 is enriched at Afadin/Nectin junctions; PAK4 depends on Afadin for junctional localization. Phosphoproteomics after PAK4 inhibitor treatment identified 17 PAK4 phosphorylation sites on junctional proteins, defining PAK4 as selective for the Afadin/nectin sub-compartment. BioID proximity labeling, quantitative mass spectrometry, co-immunoprecipitation, phosphoproteomics with PAK4 inhibitors, immunofluorescence Nature communications High 34493720
2010 PAK4 N-terminal domain associates with ribonucleoprotein (RNP) complexes and active PAK4 can affect cap-independent (IRES-mediated) translation in vivo; the N-terminal domain also contains nuclear export signals and cytoplasmic targeting elements, with endogenous PAK4 found in both cytoplasmic and nuclear fractions. Affinity chromatography, co-immunoprecipitation with RNP components, IRES-mediated translation reporter assay, subcellular fractionation Journal of cellular physiology Medium 20578242
2018 VIP and secretin activate PAK4 in pancreatic acinar cells via cAMP pathways (VIP via EPAC; secretin via PKA), and PAK4 activation is required for subsequent Na+,K+-ATPase activation and pancreatic fluid secretion. Selective cAMP pathway inhibitors (KT-5720, PKI, ESI-09, HJC0197), PAK4 inhibitors (PF-3758309, LCH-7749944), PAK4 kinase activity assay, Na+,K+-ATPase activity assay American journal of physiology. Gastrointestinal and liver physiology Medium 30520694

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia. The EMBO journal 309 9822598
2001 Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines. The Journal of biological chemistry 234 11668177
2001 The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis. The Journal of biological chemistry 186 11278822
2001 Activated PAK4 regulates cell adhesion and anchorage-independent growth. Molecular and cellular biology 153 11313478
2003 PAK4 kinase is essential for embryonic viability and for proper neuronal development. Molecular and cellular biology 131 14517283
2019 PAK4 inhibition improves PD-1 blockade immunotherapy. Nature cancer 126 34368780
2016 Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. Molecular cancer therapeutics 125 27390344
2008 A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF. Cellular signalling 123 18424072
2011 Nucleo-cytoplasmic shuttling of PAK4 modulates β-catenin intracellular translocation and signaling. Biochimica et biophysica acta 121 22173096
2020 Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma. Nature cancer 110 35121889
2008 Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification. Cancer biology & therapy 107 18836286
2014 The metastasis suppressor NDRG1 modulates the phosphorylation and nuclear translocation of β-catenin through mechanisms involving FRAT1 and PAK4. Journal of cell science 98 24829151
2007 Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs. Structure (London, England : 1993) 97 17292838
2003 Death receptor-induced activation of initiator caspase 8 is antagonized by serine/threonine kinase PAK4. Molecular and cellular biology 91 14560027
2010 PAK4: a pluripotent kinase that regulates prostate cancer cell adhesion. Journal of cell science 89 20406887
2012 Knockdown of PAK4 or PAK1 inhibits the proliferation of mutant KRAS colon cancer cells independently of RAF/MEK/ERK and PI3K/AKT signaling. Molecular cancer research : MCR 88 23233484
2018 miR-199a-3p Modulates MTOR and PAK4 Pathways and Inhibits Tumor Growth in a Hepatocellular Carcinoma Transgenic Mouse Model. Molecular therapy. Nucleic acids 85 29858083
2014 PAK4 confers cisplatin resistance in gastric cancer cells via PI3K/Akt- and MEK/ERK-dependent pathways. Bioscience reports 84 27919028
2005 PAK4 functions in tumor necrosis factor (TNF) alpha-induced survival pathways by facilitating TRADD binding to the TNF receptor. The Journal of biological chemistry 81 16227624
2016 Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma. Molecular cancer therapeutics 76 28062705
2011 Overexpression of a novel activator of PAK4, the CDK5 kinase-associated protein CDK5RAP3, promotes hepatocellular carcinoma metastasis. Cancer research 76 21385901
2012 Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma. Cell death & disease 72 23254288
2019 PAK4 signaling in health and disease: defining the PAK4-CREB axis. Experimental & molecular medicine 70 30755582
2020 Exosome-mediated RNAi of PAK4 prolongs survival of pancreatic cancer mouse model after loco-regional treatment. Biomaterials 66 32977209
2012 MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells. Biochemical and biophysical research communications 66 22766504
2015 p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling. Cancer letters 65 26546043
2015 PAK4 promotes kinase-independent stabilization of RhoU to modulate cell adhesion. The Journal of cell biology 61 26598620
2017 Zic2 promotes tumor growth and metastasis via PAK4 in hepatocellular carcinoma. Cancer letters 59 28577975
2017 A novel orally bioavailable compound KPT-9274 inhibits PAK4, and blocks triple negative breast cancer tumor growth. Scientific reports 58 28198380
2016 PAK4 Methylation by SETD6 Promotes the Activation of the Wnt/β-Catenin Pathway. The Journal of biological chemistry 56 26841865
2015 An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nature communications 56 26607847
2011 Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma. Carcinogenesis 56 21325635
2010 Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B. Molecular biology of the cell 56 20631255
2017 Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors. Journal of medicinal chemistry 55 29190083
2013 PAK4 kinase-mediated SCG10 phosphorylation involved in gastric cancer metastasis. Oncogene 55 23893240
2006 PAK4 and alphaPIX determine podosome size and number in macrophages through localized actin regulation. Journal of cellular physiology 55 16897755
2013 Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis. Oncogene 53 23934187
2017 PAK4 regulates G6PD activity by p53 degradation involving colon cancer cell growth. Cell death & disease 52 28542136
2015 MiR-199a/b-3p suppresses migration and invasion of breast cancer cells by downregulating PAK4/MEK/ERK signaling pathway. IUBMB life 52 26399456
2015 PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway. Diagnostic pathology 51 26411419
2009 Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma. Cancer science 51 19594544
2021 CDK15 promotes colorectal cancer progression via phosphorylating PAK4 and regulating β-catenin/ MEK-ERK signaling pathway. Cell death and differentiation 50 34262144
2017 A novel interaction of PAK4 with PPARγ to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma. Oncogene 46 28534509
2021 Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model. Journal of neuroinflammation 45 34275493
2013 Systems-wide analysis of K-Ras, Cdc42, and PAK4 signaling by quantitative phosphoproteomics. Molecular & cellular proteomics : MCP 43 23608596
2013 The Pak4 protein kinase is required for oncogenic transformation of MDA-MB-231 breast cancer cells. Oncogenesis 43 23732710
2019 A novel PAK4-CEBPB-CLDN4 axis involving in breast cancer cell migration and invasion. Biochemical and biophysical research communications 39 30808546
2014 The serine-threonine protein kinase PAK4 is dispensable in zebrafish: identification of a morpholino-generated pseudophenotype. PloS one 38 24945275
2013 SH3RF2 functions as an oncogene by mediating PAK4 protein stability. Carcinogenesis 38 24130170
2018 MiR-199a/b-3p inhibits gastric cancer cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway. BMC cancer 37 29304764
2018 A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells. Oncogene 37 30177834
2017 PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration. Scientific reports 37 28205613
2015 Glioblastomas require integrin αvβ3/PAK4 signaling to escape senescence. Cancer research 36 26297735
2008 MKP1 regulates the induction of MUC5AC mucin by Streptococcus pneumoniae pneumolysin by inhibiting the PAK4-JNK signaling pathway. The Journal of biological chemistry 36 18782768
2019 PAK4, a target of miR-9-5p, promotes cell proliferation and inhibits apoptosis in colorectal cancer. Cellular & molecular biology letters 35 31728150
2012 P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring. Oncogene 34 22450748
2012 PAK4-6 in cancer and neuronal development. Cellular logistics 33 23125951
2020 Targeting PAK4 Inhibits Ras-Mediated Signaling and Multiple Oncogenic Pathways in High-Risk Rhabdomyosarcoma. Cancer research 32 33168646
2018 CDC42 binds PAK4 via an extended GTPase-effector interface. Proceedings of the National Academy of Sciences of the United States of America 32 29295922
2017 Targeting Rho GTPase effector p21 activated kinase 4 (PAK4) suppresses p-Bad-microRNA drug resistance axis leading to inhibition of pancreatic ductal adenocarcinoma proliferation. Small GTPases 32 28641032
2014 p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines. Cancer research and treatment 32 25672581
2019 miR-193a-3p inhibition of the Slug activator PAK4 suppresses non-small cell lung cancer aggressiveness via the p53/Slug/L1CAM pathway. Cancer letters 30 30685413
2018 Dual PAK4-NAMPT Inhibition Impacts Growth and Survival, and Increases Sensitivity to DNA-Damaging Agents in Waldenström Macroglobulinemia. Clinical cancer research : an official journal of the American Association for Cancer Research 30 30206161
2011 A key role for Pak4 in proliferation and differentiation of neural progenitor cells. Developmental biology 30 21382368
2022 PAK4 in cancer development: Emerging player and therapeutic opportunities. Cancer letters 29 35798086
2019 PAK4 Phosphorylates Fumarase and Blocks TGFβ-Induced Cell Growth Arrest in Lung Cancer Cells. Cancer research 29 30683654
2020 KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells. Chemical research in toxicology 28 31876149
2019 Targeting XPO1 and PAK4 in 8505C Anaplastic Thyroid Cancer Cells: Putative Implications for Overcoming Lenvatinib Therapy Resistance. International journal of molecular sciences 28 31905765
2019 Nonconserved miR-608 suppresses prostate cancer progression through RAC2/PAK4/LIMK1 and BCL2L1/caspase-3 pathways by targeting the 3'-UTRs of RAC2/BCL2L1 and the coding region of PAK4. Cancer medicine 26 31389670
2014 MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4). Molecular and cellular biochemistry 26 25410752
2020 Therapeutically actionable PAK4 is amplified, overexpressed, and involved in bladder cancer progression. Oncogene 25 32231273
2016 Nigral dopaminergic PAK4 prevents neurodegeneration in rat models of Parkinson's disease. Science translational medicine 25 27903866
2017 Simvastatin Attenuates Acute Lung Injury via Regulating CDC42-PAK4 and Endothelial Microparticles. Shock (Augusta, Ga.) 24 27513084
2020 Effects of PAK4/LIMK1/Cofilin-1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells. Journal of clinical laboratory analysis 23 32463132
2019 PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer. Cancer letters 23 31121213
2018 Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of Na+,K+-ATPase in pancreatic acinar cells. American journal of physiology. Gastrointestinal and liver physiology 23 30520694
2017 Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization. Oncotarget 22 29100370
2012 The pak4 protein kinase in breast cancer. ISRN oncology 22 23326684
2011 Role for p21-activated kinase PAK4 in development of the mammalian heart. Transgenic research 22 22173944
2022 Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells. Acta pharmaceutica Sinica. B 21 35755272
2021 The role of PAK4 in the immune system and its potential implication in cancer immunotherapy. Cellular immunology 21 34246086
2021 A novel PAK4 inhibitor suppresses pancreatic cancer growth and enhances the inhibitory effect of gemcitabine. Translational oncology 21 34973571
2020 LINC01224 Exhibits Cancer-Promoting Activity in Epithelial Ovarian Cancer Through microRNA-485-5p-Mediated PAK4 Upregulation. OncoTargets and therapy 21 32606778
2015 Functional cross-talk between Cdc42 and two downstream targets, Par6B and PAK4. The Biochemical journal 21 25662318
2025 Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4. Communications biology 20 39833606
2024 Development of a PAK4-targeting PROTAC for renal carcinoma therapy: concurrent inhibition of cancer cell proliferation and enhancement of immune cell response. EBioMedicine 20 38810561
2020 Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways. Drug design, development and therapy 20 32158195
2018 Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors. European journal of medicinal chemistry 20 29886323
2017 Discovery of indolin-2-one derivatives as potent PAK4 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study. Bioorganic & medicinal chemistry 20 28502459
2017 MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4. International journal of oncology 20 29048626
2020 Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4. OncoTargets and therapy 19 32158221
2017 Development of 2, 4-diaminoquinazoline derivatives as potent PAK4 inhibitors by the core refinement strategy. European journal of medicinal chemistry 19 28284095
2016 (-)-β-hydrastine suppresses the proliferation and invasion of human lung adenocarcinoma cells by inhibiting PAK4 kinase activity. Oncology reports 19 26821251
2015 Design, synthesis and biological evaluation of 1-phenanthryl-tetrahydroisoquinoline derivatives as novel p21-activated kinase 4 (PAK4) inhibitors. Organic & biomolecular chemistry 19 25705811
2010 N-terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals. Journal of cellular physiology 18 20578242
2020 PAK4 methylation by the methyltransferase SETD6 attenuates cell adhesion. Scientific reports 17 33051544
2015 microRNA-126 suppresses PAK4 expression in ovarian cancer SKOV3 cells. Oncology letters 17 26137045
2016 Pak4 Is Required during Epithelial Polarity Remodeling through Regulating AJ Stability and Bazooka Retention at the ZA. Cell reports 16 27052178
2021 PAK4 suppresses motor neuron degeneration in hSOD1G93A -linked amyotrophic lateral sclerosis cell and rat models. Cell proliferation 14 33615605
2021 Proximity proteomics identifies PAK4 as a component of Afadin-Nectin junctions. Nature communications 14 34493720