Affinage

PAK4

Serine/threonine-protein kinase PAK 4 · UniProt O96013

Length
591 aa
Mass
64.1 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 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

PAK4 is a Cdc42-activated serine/threonine kinase that couples Rho-family GTPase signaling to actin cytoskeleton remodeling, cell adhesion turnover, anti-apoptotic signaling, and transcriptional control (PMID:9822598, PMID:11313478). It was first defined as a Cdc42 effector whose GTPase-binding domain engages GTP-loaded Cdc42, redirecting PAK4 to the Golgi and driving filopodia and actin polymerization through its kinase activity (PMID:9822598); structural work later showed that full-length PAK4 forms a compact heterodimer with CDC42 in which kinase C-lobe and polybasic contacts beyond the canonical CRIB interface tune activity and binding affinity (PMID:29295922), and that catalytic output is held in check by the endogenous inhibitor Inka1 (PMID:26607847). Activation requires autophosphorylation at Ser474, with the N-terminal region acting as a negative regulator that is relieved by HGF/PI3K signaling (PMID:11668177, PMID:12244132). A core cytoskeletal program runs through PAK4 phosphorylation of LIMK1, which in turn phosphorylates cofilin to remodel actin and promote migration (PMID:11413130, PMID:18424072), and through phosphorylation of GEF-H1 (Ser810) and paxillin (Ser272) to control RhoA activity, stress fibers, and focal-adhesion turnover (PMID:15827085, PMID:20406887). PAK4 also drives adhesion turnover kinase-independently by stabilizing RhoU against Rab40A–Cullin5-mediated degradation (PMID:26598620) and localizes to cell-cell junctions, podosomes, and the mitotic spindle, where it is required for astral microtubule organization and dynein/dynactin positioning (PMID:22450748, PMID:26068882, PMID:31825823). As a nucleo-cytoplasmic shuttling protein, PAK4 enters the nucleus to phosphorylate β-catenin (Ser675) and promote TCF/LEF transcription, an axis amplified by SETD6-mediated methylation at K473 (PMID:22173096, PMID:26841865, PMID:33051544). PAK4 broadly suppresses tumor-suppressor and growth-arrest programs, phosphorylating p53 (Ser215), Smad2 (Ser465), fumarase (Ser46), and RELB (Ser151), and regulating p21 to control cell-cycle progression and senescence (PMID:21381077, PMID:23934187, PMID:27496712, PMID:31399573, PMID:30683654). PAK4 is essential for mouse embryonic development, with knockouts dying by E11.5 from cardiac, neuronal, and neural-tube defects (PMID:14517283).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Established PAK4's founding identity by answering whether it is a Cdc42 effector and how GTPase binding reroutes it to drive actin remodeling.

    Evidence GBD interaction assays with activated Cdc42Hs, Golgi localization and kinase-dead mutant analysis by immunofluorescence

    PMID:9822598

    Open questions at the time
    • Direct cytoskeletal substrates not yet identified
    • Mechanism linking Golgi localization to filopodia formation unresolved
  2. 2001 High

    Defined how PAK4 catalytic activity is switched on and showed its kinase function is required for oncogenic transformation.

    Evidence Site-directed mutagenesis identifying Ser474 autophosphorylation, phospho-specific antibody, NIH3T3 transformation and anchorage-independent growth assays

    PMID:11668177

    Open questions at the time
    • Upstream kinases/regulators of activation not defined
    • Relationship of autophosphorylation to N-terminal autoinhibition unresolved
  3. 2001 High

    Connected PAK4 to the actin cytoskeleton mechanistically and to cell survival, defining its first substrate (LIMK1) and first anti-apoptotic readout (Bad).

    Evidence In vitro kinase and binding assays, dominant-negative cofilin/LIMK1 rescue, apoptosis assays with TNF-α/UV/serum starvation and Bad phosphorylation/caspase readouts

    PMID:11278822 PMID:11313478 PMID:11413130

    Open questions at the time
    • Whether PAK4 phosphorylates Bad directly not established
    • Quantitative contribution of LIMK1 vs other effectors to cytoskeletal change unclear
  4. 2002 High

    Placed PAK4 in a growth-factor signaling cascade and revealed intramolecular autoinhibition by mapping HGF/PI3K-dependent activation and N-terminal repression.

    Evidence HGF stimulation in MDCK cells, LY294002 PI3K inhibition, kinase activity assays, truncation mutant analysis

    PMID:12244132

    Open questions at the time
    • Direct biochemical link between PI3K products and PAK4 not shown
    • Identity of the relieving signal acting on the N-terminus undefined
  5. 2003 High

    Demonstrated PAK4 is physiologically essential and separated its kinase-dependent from kinase-independent survival functions.

    Evidence PAK4 knockout mouse with developmental phenotyping; kinase-dead mutant analysis of caspase-8 inhibition

    PMID:14517283 PMID:14560027

    Open questions at the time
    • In vivo embryonic phenotype not assigned to specific substrates
    • Proposed caspase-8 recruitment inhibition not directly demonstrated
  6. 2005 Medium

    Elucidated how PAK4 reorganizes actin architecture by identifying GEF-H1 as a substrate that links PAK4 to RhoA-dependent stress fiber regulation, while linking PAK4 to senescence control.

    Evidence Co-IP, domain mapping of the GID, in vitro phosphorylation of GEF-H1 Ser810, microtubule release assay; senescence assays with ERK inhibition and p16/p19 analysis

    PMID:15827085 PMID:16227603

    Open questions at the time
    • GEF-H1 Ser810 phospho-site role in vivo not tested
    • Senescence pathway analysis single-lab and pharmacology-dependent
  7. 2006 Medium

    Extended PAK4's cytoskeletal role to specialized adhesion structures by showing kinase-dependent control of podosomes.

    Evidence shRNA knockdown, kinase/truncation mutants and quantitative podosome imaging in primary human macrophages

    PMID:16897755

    Open questions at the time
    • Podosome substrate(s) at the structure not identified
    • Single-lab observation
  8. 2008 High

    Validated the PAK4-LIMK1-cofilin axis as a direct, spatially-resolved interaction driving cancer cell migration.

    Evidence FRET-FLIM live-cell imaging, Co-IP, cofilin phosphorylation and migration assays in prostate cancer cells

    PMID:18319301 PMID:18424072

    Open questions at the time
    • Vascular morphogenesis role (lumen formation) relies on dominant-negative/RNAi without substrate
    • Spatial control of LIMK1 engagement at foci mechanistically incomplete
  9. 2009 High

    Expanded PAK4's adaptor/scaffolding repertoire by identifying kinase-independent interactions (Gab1, DGCR6L) that organize migration and invasion machinery.

    Evidence Co-IP, domain mapping, interaction-deficient mutants, LIMK1/cofilin phosphorylation and invasion assays

    PMID:19289496 PMID:19778628

    Open questions at the time
    • DGCR6L interaction Medium-confidence and single-lab
    • How scaffolding integrates with catalytic LIMK1 activation unclear
  10. 2010 High

    Defined PAK4's role at focal adhesions by identifying paxillin Ser272 as a substrate coupled to RhoA/GEF-H1-mediated adhesion turnover.

    Evidence Co-IP, in vitro kinase assay, focal-adhesion immunofluorescence, siRNA and RhoA activity assay in prostate cancer cells

    PMID:20406887

    Open questions at the time
    • Hierarchy of paxillin vs GEF-H1 phosphorylation in adhesion turnover unresolved
    • N-terminal RNP/IRES-translation role (Low confidence) not corroborated
  11. 2011 High

    Revealed nuclear PAK4 as a transcriptional regulator by mapping its shuttling signals and β-catenin Ser675 phosphorylation, and identified upstream stabilizers/activators (CDK5RAP3) and cell-cycle control via p21.

    Evidence NLS/NES mutagenesis, CRM-1/importin-α5 manipulation, β-catenin phosphorylation, TCF/LEF reporter and ChIP; Co-IP and kinase assays for CDK5RAP3; cell-cycle synchronization with p21 readout in knockout cells

    PMID:21381077 PMID:21385901 PMID:22173096

    Open questions at the time
    • Signals triggering nuclear import in physiological contexts not defined
    • Mechanism of p21 degradation control by PAK4 unclear
  12. 2012 Medium

    Identified an unanticipated mitotic role by showing PAK4 is required for spindle anchoring and dynein/dynactin positioning.

    Evidence siRNA depletion, live imaging, kinetochore/astral MT immunofluorescence and dynein/dynactin localization analysis

    PMID:22450748

    Open questions at the time
    • Mitotic substrate(s) of PAK4 not identified
    • Single-lab RNAi phenotype
  13. 2013 High

    Broadened PAK4 substrate scope into TGF-β/Smad signaling, microtubule-regulating SCG10, and protein-stability control, establishing dual kinase-dependent/independent regulation of tumor-suppressive pathways.

    Evidence Co-IP, kinase and kinase-dead assays, Smad2 Ser465 phosphorylation and TGF-β reporter; SCG10 Ser50 in vitro kinase assay with inhibitor/RNAi and xenograft; SH3RF2 ubiquitination/stabilization assays

    PMID:23893240 PMID:23934187 PMID:24130170

    Open questions at the time
    • Switch governing kinase-dependent vs independent Smad regulation undefined
    • SH3RF2 stabilization mechanism single-lab
  14. 2015 High

    Consolidated PAK4's dual catalytic/non-catalytic adhesion and polarity functions and provided the first structural view of the catalytic domain.

    Evidence Kinase-dead and Cdc42-binding mutant rescue with RhoU stabilization and ubiquitination assays; Par6B Ser143 kinase assay; junction localization and centrosome reorientation; αvβ3-PAK4 senescence in GBM; in cellulo crystallography of PAK4-Inka1

    PMID:25662318 PMID:26068882 PMID:26297735 PMID:26598620 PMID:26607847

    Open questions at the time
    • Integration of kinase-dependent and RhoU-stabilizing roles in single cells unclear
    • Tissue-specificity of PAK4-driven senescence escape mechanistically incomplete
  15. 2016 High

    Established PAK4 as a methylation-regulated suppressor of p53 and amplifier of Wnt/β-catenin transcription, linking it to metabolic reprogramming.

    Evidence In vitro methylation, ChIP, β-catenin Co-IP and reporter assays; p53 Ser215 in vitro kinase assay and reporter; G6PD interaction and Mdm2/p53 ubiquitination assays

    PMID:26841865 PMID:27496712 PMID:28542136

    Open questions at the time
    • SETD6 methylation site not yet mapped at this stage
    • Direct vs indirect p53 destabilization mechanisms overlap unresolved
  16. 2018 High

    Resolved the full-length PAK4-CDC42 architecture and expanded transcriptional/signaling substrates (CEBPB) and upstream activators (VIP/secretin via EPAC/PKA), plus ERα corepression.

    Evidence X-ray crystallography and SAXS with kinase assays; CEBPB Thr235 phosphorylation and CLDN4 promoter assays; EPAC/PKA pharmacology with PAK4 and Na+,K+-ATPase activity; ERα Co-IP, nuclear co-translocation and metastasis model

    PMID:29295922 PMID:30177834 PMID:30520694 PMID:30808546

    Open questions at the time
    • How distinct cAMP effectors converge on PAK4 activation unclear
    • ERα corepression Medium-confidence single-lab
  17. 2019 High

    Defined a coherent PAK4 program antagonizing growth arrest/senescence (RELB, fumarase, p21) while extending substrates into EMT (Slug) and neuroprotection (CRTC1).

    Evidence RELB Ser151 phospho-mutagenesis, DNA-binding and transgenic mouse; fumarase Ser46 kinase assay, 14-3-3 Co-IP and p21 ChIP; Slug phosphorylation with miR-193a-3p; CRTC1 Ser215 phospho-mutant rescue in rodent PD models; podosome-ring kinase requirement with superresolution

    PMID:27903866 PMID:30683654 PMID:30685413 PMID:31399573 PMID:31825823

    Open questions at the time
    • Slug phosphorylation site not mapped
    • Tissue-specific switching between pro-survival and neuroprotective outputs unexplained
  18. 2020 High

    Demonstrated PAK4's roles in the tumor microenvironment and its regulation by an upstream kinase, integrating transcriptomic reprogramming with metastatic and proliferative signaling.

    Evidence Endothelial PAK4 knockout with MEF2D/ZEB1/SLUG and adhesion-molecule analysis and T-cell infiltration in GBM models; SETD6 K473 methylation mutagenesis with β-catenin/paxillin readouts; CDK15-PAK4 Ser291 kinase assay with KO mouse and xenograft models

    PMID:33051544 PMID:34262144 PMID:35121889

    Open questions at the time
    • Endothelial transcriptome reprogramming mechanism downstream of PAK4 incompletely mapped
    • Interplay between K473 methylation and S291 phosphorylation in activity control untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse upstream inputs (GTPases, growth factors, cAMP effectors, methylation, S291 phosphorylation) are integrated to direct PAK4 toward specific subcellular pools and substrate sets remains unresolved.
  • No unified model linking activation mode to substrate selection
  • Substrates for mitotic spindle and podosome functions unidentified
  • Relative contribution of kinase-dependent vs scaffolding functions in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 6 GO:0098772 molecular function regulator activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 3 GO:0005856 cytoskeleton 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CDC42CTNNB1GAB1GEF-H1LIMK1PXNSETD6SMAD2

Evidence

Reading pass · 46 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 specifically with the activated (GTP-bound) form of Cdc42Hs through its GTPase-binding domain (GBD). Co-expression with constitutively active Cdc42HsV12 redistributed PAK4 to the brefeldin A-sensitive Golgi compartment and induced filopodia and actin polymerization in a manner dependent on PAK4 kinase activity. Co-expression, GBD interaction assays, brefeldin A-sensitive Golgi localization experiments, kinase-dead mutant analysis, immunofluorescence The EMBO journal High 9822598
2001 Serine 474 in the PAK4 kinase domain was identified as the autophosphorylation site in vivo. Mutation S474E produces constitutively active PAK4, and phospho-S474-specific antibodies detect activated PAK4 on the Golgi membrane when PAK4 is co-expressed with activated Cdc42. A kinase-inactive mutant (K350A,K351A) blocked Ras-driven transformation. Site-directed mutagenesis, phospho-specific antibody, immunofluorescence, NIH3T3 transformation assay, HCT116 anchorage-independent growth assay The Journal of biological chemistry High 11668177
2001 PAK4 interacts specifically with LIM kinase 1 (LIMK1) and phosphorylates it more strongly than PAK1 does. Activated PAK4 stimulates LIMK1's ability to phosphorylate cofilin, and dominant-negative LIMK1 and a phosphorylation-resistant cofilin mutant inhibit PAK4-induced cytoskeletal and cell shape changes. Binding assays, immune complex kinase assays, dominant-negative mutant rescue, immunofluorescence in C2C12 cells The Journal of biological chemistry High 11413130
2001 PAK4 protects cells from apoptosis: expression of wild-type or constitutively active PAK4 delays apoptosis in response to TNF-α, UV irradiation, and serum starvation. PAK4 expression increases phosphorylation of the proapoptotic protein Bad and inhibits caspase activation. Overexpression of WT and constitutively active PAK4, apoptosis assays (TNF-α, UV, serum starvation), Bad phosphorylation assay, caspase activity assay The Journal of biological chemistry High 11278822
2001 Activated PAK4 dissolves actin stress fibers and focal adhesions, impairs cell spreading on fibronectin, and confers anchorage independence (soft agar colony formation). Dominant-negative PAK4 mutants inhibit focus formation by oncogenic Dbl, establishing PAK4 as a transforming kinase downstream of Rho GTPase exchange factors. Constitutively active PAK4 mutant expression, fibronectin adhesion assay, soft agar colony assay, dominant-negative inhibition of Dbl-induced focus formation Molecular and cellular biology High 11313478
2002 PAK4 is activated by HGF in epithelial (MDCK) cells downstream of PI3K; LY294002 (PI3K inhibitor) blocks HGF-induced PAK4 kinase activation and relocalization to the cell periphery. The isolated C-terminal kinase domain can induce cell rounding in the presence of LY294002, indicating the N-terminal region acts as a negative regulator of PAK4 activity. HGF stimulation, LY294002 PI3K inhibitor, PAK4 kinase activity assay, truncation mutant analysis, immunofluorescence Journal of cell science High 12244132
2003 PAK4 is essential for embryonic viability: PAK4 knockout mice die by embryonic day 11.5 with defects in heart development, neuronal differentiation and migration, and neural tube folding, demonstrating an essential in vivo role for PAK4 in cytoskeletal regulation and cell/ECM adhesion during development. Gene targeting (PAK4 knockout mouse), histological and morphological analysis of PAK4-null embryos Molecular and cellular biology High 14517283
2003 PAK4 inhibits the activation of initiator caspase 8 downstream of death domain-containing receptors (TNF receptor, Fas receptor), independently of its kinase activity, potentially by inhibiting caspase 8 recruitment to death domain receptors. This is distinct from PAK4's kinase-dependent phosphorylation of Bad. PAK4 overexpression, kinase-dead mutant, caspase 8 activation assay, TNF/Fas receptor stimulation Molecular and cellular biology Medium 14560027
2005 PAK4 mediates morphological changes through association with the Rho-family GEF, GEF-H1, via a novel GEF-H1 interaction domain (GID) in PAK4. PAK4 phosphorylates GEF-H1 at Ser810 to block stress fiber formation and promote lamellipodia. PAK4 phosphorylation of MT-bound GEF-H1 releases it into the cytoplasm, coinciding with stress fiber dissolution. Co-immunoprecipitation, domain mapping, in vitro phosphorylation assay, immunofluorescence, microtubule association assay in NIH-3T3 cells Journal of cell science High 15827085
2005 Activated PAK4 induces premature senescence in primary fibroblasts via a pathway requiring ERK MAPK and the cell cycle inhibitors p16(INK4) and p19(ARF). PAK4 expression levels are upregulated in response to senescence-promoting stimuli. Activated PAK4 expression in primary fibroblasts, senescence assay, ERK inhibitor treatment, p16/p19 pathway analysis Molecular and cellular biology Medium 16227603
2006 PAK4 regulates podosome size and number in primary human macrophages: shRNA knockdown or PAK4 truncation mutants reduce podosome numbers, kinase-active PAK4 enhances podosome size, and kinase-inactive PAK4 reduces podosome size, demonstrating a kinase activity-dependent role in localized actin dynamics at podosomes. shRNA knockdown, PAK4 truncation and kinase mutant expression, immunofluorescence, actin structure analysis in primary human macrophages Journal of cellular physiology Medium 16897755
2008 PAK4 binds to and phosphorylates LIMK1 in an HGF-dependent manner in prostate cancer cells. PAK4-LIMK1 direct interaction was visualized in living cells by FRET-FLIM, concentrated in peripheral foci. Variations in PAK4 expression change cofilin phosphorylation levels, correlated with LIMK1 activity and cell migration speed; PAK4 and LIMK1 act synergistically to increase migration. Co-immunoprecipitation, FRET-FLIM imaging, cofilin phosphorylation assays, PAK4 siRNA knockdown, cell migration assays Cellular signalling High 18424072
2008 RNAi or dominant-negative suppression of PAK4 markedly inhibits endothelial cell lumen and tube formation in 3D collagen matrices. PAK4 phosphorylation correlates with lumenogenesis in a PKC-dependent manner, placing PAK4 downstream of Cdc42/Rac1 and PKC in vascular morphogenesis. RNAi knockdown, dominant-negative expression, 3D collagen matrix lumen formation assay, PKC inhibitor treatment Journal of cell science Medium 18319301
2009 PAK4 is a novel Gab1-interacting protein; upon HGF stimulation, Gab1 and PAK4 associate and colocalize at lamellipodia. The interaction is mediated through the GEF-interacting domain of PAK4 and a novel Gab1 region, requires Gab1 phosphorylation but not PAK4 kinase activity. Gab1-Pak4 association is required for HGF-induced cell dispersal, migration, and invasion. Co-immunoprecipitation, domain mapping, confocal colocalization, Gab1 mutant unable to recruit Pak4, cell dispersal and invasion assays Molecular and cellular biology High 19289496
2009 DGCR6L is a novel PAK4-binding protein, confirmed by GST pulldown and co-immunoprecipitation. L115 of DGCR6L is critical for binding to the C-terminus (aa 466–572) of PAK4. DGCR6L is required for formation of a PAK4-DGCR6L-β-actin complex and enhances phosphorylation of LIMK1 and cofilin in a dose-dependent manner to promote gastric cancer cell migration. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, site-directed mutagenesis (L115V), LIMK1/cofilin phosphorylation assay, migration assay The international journal of biochemistry & cell biology Medium 19778628
2010 PAK4 phosphorylates paxillin at serine 272, co-immunoprecipitates with paxillin, localizes to focal adhesions, and regulates RhoA activity via GEF-H1 to control actin cytoskeletal rearrangement and focal adhesion turnover. PAK4-depleted prostate cancer cells show increased focal adhesion size/number and reduced adhesion turnover rates. Co-immunoprecipitation, in vitro kinase assay, immunofluorescence localization to focal adhesions, PAK4 siRNA knockdown, RhoA activity assay Journal of cell science High 20406887
2011 PAK4 is a nucleo-cytoplasmic shuttling protein with three nuclear export signals (NESs) and two nuclear localization signals (NLSs). It is exported via CRM-1-dependent pathway and imported in an importin α5-dependent manner. Nuclear PAK4 phosphorylates β-catenin at Ser675, promoting TCF/LEF transcriptional activity, stabilizing β-catenin by inhibiting its degradation, and associating with the TCF/LEF transcriptional complex. NLS/NES mutagenesis, CRM-1/importin α5 inhibition/knockdown, β-catenin phosphorylation assay, TCF/LEF reporter assay, ChIP assay Biochimica et biophysica acta High 22173096
2011 CDK5RAP3 (C53/LZAP) is a novel binding partner of PAK4 that enhances PAK4 kinase activity. siRNA-mediated knockdown of PAK4 in CDK5RAP3-overexpressing HCC cells reversed the enhanced cell invasiveness, demonstrating that PAK4 activity is required for CDK5RAP3-promoted metastasis. Co-immunoprecipitation, PAK4 kinase activity assay, siRNA knockdown, invasion assay Cancer research Medium 21385901
2011 PAK4 levels peak transiently in early G1 phase of the cell cycle. PAK4 deletion increases p21 levels and is required for normal p21 degradation. Absence of PAK4 in serum-starved cells reduces the fraction of cells in G1 and increases G2/M cells, indicating PAK4 controls cell cycle progression partly by regulating p21 levels. Cell cycle synchronization, flow cytometry, PAK4 knockout cells, p21 protein level analysis Journal of cellular biochemistry Medium 21381077
2012 PAK4 is required for metaphase spindle positioning and anchoring. PAK4-depleted cells show defective astral microtubule networks, spindle miscentering, cortical membrane blebbing during prometaphase, and mislocalization of dynein/dynactin complex components at kinetochores and on astral MTs, resulting in prolonged metaphase-like arrest and eventual cohesion fatigue. PAK4 siRNA depletion, live cell imaging, immunofluorescence of spindle/kinetochore markers, dynein/dynactin localization analysis Oncogene Medium 22450748
2013 PAK4 interacts with Smad2/3 and modulates their phosphorylation via both kinase-dependent and kinase-independent mechanisms to attenuate Smad2/3 axis transactivation and TGF-β-mediated growth inhibition. PAK4 blocks TGF-β1-induced phosphorylation of Smad2 Ser465/467 independently of kinase activity, and phosphorylates Smad2 on Ser465 (promoting Smad2 degradation via ubiquitin-proteasome pathway) under HGF stimulation. Co-immunoprecipitation, kinase assay, kinase-dead mutant, TGF-β reporter assay, ubiquitin-proteasome pathway analysis, HGF stimulation Oncogene Medium 23934187
2013 PAK4 phosphorylates SCG10 (superior cervical ganglia 10) at serine 50 (Ser50). Phosphorylated SCG10 regulates microtubule dynamics to promote gastric cancer cell migration and invasion, and blocking PAK4 (by inhibitor LCH-7749944 or RNAi) inhibits Ser50 phosphorylation and cell invasion. In vitro kinase assay, site-directed mutagenesis (S50A), PAK4 inhibitor LCH-7749944, RNAi, cell invasion assay, xenograft mouse model Oncogene High 23893240
2013 SH3RF2 inhibits PAK4 ubiquitination and proteasomal degradation via physical interaction-mediated steric hindrance, thereby stabilizing PAK4 protein levels and promoting oncogenic signaling. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, SH3RF2 overexpression/ablation Carcinogenesis Medium 24130170
2015 PAK4 drives cell adhesion turnover in a kinase-independent manner by stabilizing RhoU protein levels. PAK4 protects RhoU from ubiquitination by the Rab40A-Cullin 5 E3 ligase complex. RhoU overexpression rescues the PAK4-depletion adhesion phenotype, and loss of RhoU reduces adhesion turnover and migration. PAK4 knockdown, kinase-dead PAK4 rescue, Cdc42-binding mutant rescue, RhoU overexpression rescue, ubiquitination assay, Rab40A-Cullin 5 complex identification The Journal of cell biology High 26598620
2015 PAK4 phosphorylates Par6B at Ser143, blocking Par6B's interaction with Cdc42, providing a mechanism to control Par6B subcellular localization and interactions in epithelial polarity establishment. Both PAK4 and Par6B are required for assembly of apical junctions in human bronchial epithelial cells. In vitro kinase assay, Co-immunoprecipitation, site-directed mutagenesis (Par6B S143), RNAi knockdown, apical junction assembly assay The Biochemical journal Medium 25662318
2015 PAK4 localizes primarily to cell-cell junctions (not focal adhesions or leading edge in migrating cells). PAK4 depletion or kinase inhibition (PF-3758309) does not affect collective migration but causes defects in centrosome reorientation after wounding. PAK4 phosphorylates β-catenin at Ser-675 predominantly at cell-cell junctions. Immunofluorescence localization, PAK4 siRNA knockdown, PF-3758309 inhibitor, wound-healing centrosome reorientation assay, β-catenin phosphorylation assay PloS one Medium 26068882
2015 Integrin αvβ3 recruits and activates PAK4 to allow glioblastoma cells to evade oncogene-induced senescence. Targeting either αvβ3 or PAK4 triggers a p21-dependent, p53-independent senescence phenotype in GBM cells specifically; this dependence is tissue-specific (not found in epithelial cancers) and other PAK family members are not required. αvβ3 integrin targeting, PAK4 knockdown, senescence assay, p21/p53 genetic analysis in GBM vs. epithelial cancer cells Cancer research Medium 26297735
2015 The crystal structure of human PAK4 catalytic domain in complex with its endogenous inhibitor Inka1 was determined at 2.95 Å resolution using in cellulo crystals from single mammalian cells. The structure reveals details of how PAK4 binds cellular ATP and Inka1 at the active site. In cellulo X-ray crystallography at 2.95 Å resolution, crystal growth in mammalian cells Nature communications High 26607847
2016 SETD6 methyltransferase methylates PAK4 both in vitro and at chromatin in cells. SETD6 depletion hinders activation of Wnt/β-catenin target genes. In the presence of SETD6, physical interaction between PAK4 and β-catenin is dramatically increased, leading to enhanced transcription of β-catenin target genes. In vitro methylation assay, ChIP, SETD6 knockdown, β-catenin co-immunoprecipitation, TCF/LEF reporter assay The Journal of biological chemistry High 26841865
2016 PAK4 directly phosphorylates p53 at serine 215, attenuating p53 transcriptional transactivation activity and inhibiting p53-mediated suppression of HCC cell invasion. In vitro kinase assay, site-directed mutagenesis (S215 of p53), p53 transcriptional reporter assay, PAK4 overexpression/silencing, invasion assay in HCC cells Cancer research Medium 27496712
2016 PAK4 promotes G6PD activity and glucose reprogramming by interacting with G6PD and enhancing Mdm2-mediated p53 ubiquitination and degradation (reducing p53-mediated suppression of G6PD), leading to increased NADPH production and lipid biosynthesis in colon cancer cells. Co-immunoprecipitation, G6PD activity assay, p53 ubiquitination assay, Mdm2 interaction analysis, PAK4 knockdown/overexpression Cell death & disease Medium 28542136
2017 Zic2 transcription factor directly binds the PAK4 promoter and activates PAK4 expression, as demonstrated by ChIP and luciferase assays. PAK4 interference attenuates Zic2-mediated cell growth via the Raf/MEK/ERK pathway. ChIP assay, luciferase reporter assay, PAK4 siRNA knockdown, Raf/MEK/ERK pathway analysis Cancer letters Medium 28577975
2017 PAK4 interacts specifically with p85α (the regulatory subunit of PI3K) in pancreatic cancer cells; PAK4-deficient cells exhibit reduced Akt phosphorylation downstream of HGF, implicating a novel role for PAK4 within the PI3K/Akt pathway. Co-immunoprecipitation (PAK4-p85α), PAK4 knockdown, Akt phosphorylation assay, HGF stimulation Scientific reports Medium 28205613
2018 X-ray crystallography and solution scattering revealed that full-length PAK4 heterodimer with CDC42 adopts a compact organization. In addition to the canonical CRIB domain–CDC42 interaction, unexpected contacts involve the PAK4 kinase C-lobe, CDC42, and the PAK4 polybasic region. These additional interactions modulate kinase activity and increase CDC42 binding affinity for full-length PAK4 compared to CRIB domain alone. X-ray crystallography, small angle X-ray scattering (SAXS), kinase activity assay, binding affinity measurement Proceedings of the National Academy of Sciences of the United States of America High 29295922
2018 PAK4 phosphorylates CEBPB at Thr-235 to upregulate CLDN4 (claudin-4) expression, promoting breast cancer cell migration and invasion via a PAK4-CEBPB-CLDN4 axis. PAK4 knockdown, CEBPB phosphorylation assay, CLDN4 promoter ChIP/luciferase, rescue experiments in MDA-MB-231 and ZR-75-30 cells Biochemical and biophysical research communications Medium 30808546
2018 VIP activates PAK4 via EPAC-dependent cAMP signaling whereas secretin activates PAK4 via PKA-dependent signaling in pancreatic acinar cells. PAK4 activation is required for VIP/secretin-induced Na+,K+-ATPase activation, which mediates pancreatic fluid secretion. EPAC inhibitors (ESI-09, HJC0197), PKA inhibitors (KT-5720, PKI), PAK4 kinase activity assay, Na+,K+-ATPase activity assay, EPAC agonist American journal of physiology. Gastrointestinal and liver physiology Medium 30520694
2019 PAK4 phosphorylates RELB at Ser151, which is critical for RELB-DNA interaction and transcriptional activity. A PAK4-RELB-C/EBPβ axis controls senescence-like growth arrest in breast cancer cells, and PAK4 overexpression abrogates H-RAS-V12-induced senescence in untransformed mammary epithelial cells. PAK4 overexpression in untransformed MCF10A, PAK4 depletion in breast cancer lines, RELB phosphorylation assay, RELB-DNA binding assay (EMSA or reporter), C/EBPβ expression analysis, MMTV-PAK4 transgenic mouse model Nature communications High 31399573
2019 PAK4 directly phosphorylates fumarase (FH) at Ser46 in non-small cell lung cancer cells. PAK4-phosphorylated FH binds to 14-3-3, causing cytosolic detention of FH and preventing formation of the FH/CSL/p53 complex at the p21 promoter, thereby blocking TGF-β-induced p21 transcription and cell growth arrest. In vitro kinase assay, site-directed mutagenesis (FH S46), 14-3-3 co-immunoprecipitation, ChIP assay, p21 reporter assay, PAK4 knockdown/overexpression Cancer research High 30683654
2019 PAK4 directly phosphorylates Slug (SNAI2), leading to Slug stabilization and pro-malignant activity in NSCLC cells. miR-193a-3p targeting of PAK4 reduces downstream p-Slug and L1CAM expression, suppressing NSCLC migration and invasion. PAK4 knockdown/overexpression, Slug phosphorylation assay, miR-193a-3p overexpression, L1CAM expression analysis, migration/invasion assay Cancer letters Medium 30685413
2019 PAK4 phosphorylates CRTC1 (CREB-regulated transcription coactivator 1) at S215. Constitutively active PAK4 protects dopaminergic neurons in rodent PD models, and this neuroprotective effect is mediated by CRTC1-S215 phosphorylation driving expression of CREB targets Bcl-2, BDNF, and PGC-1α; non-phosphorylatable CRTC1(S215A) abrogates caPAK4 neuroprotection. Constitutively active PAK4 (caPAK4S445N/S474E) viral expression, CRTC1 phosphorylation assay, S215A mutant rescue, Bcl-2/BDNF/PGC-1α expression, 6-OHDA and α-synuclein rat PD models Science translational medicine High 27903866
2019 PAK4 kinase activity is essential for podosome ring formation in myeloid cells. PAK4 localizes specifically within the podosome ring by superresolution imaging. PAK4 inhibition reduces podosome formation and induces focal adhesion formation. PAK4 depletion perturbs phospho-Akt signaling at podosomes, placing PAK4 kinase activity at the podosome ring:core interface intersecting the Akt pathway. PAK4 inhibitor (PF-3758309), PAK4 siRNA knockdown, kinase-dead PAK4 rescue, superresolution (STORM/STED) imaging, podosome assay, phospho-Akt analysis Cell reports High 31825823
2020 PAK4 reprograms tumor endothelial cell transcriptome via a MEF2D/ZEB1- and SLUG-mediated mechanism, downregulating claudin-14 and VCAM-1 expression, thereby 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 (genetic), kinome-wide screening, MEF2D/ZEB1/SLUG pathway analysis, claudin-14 and VCAM-1 expression assay, T cell adhesion assay, GBM mouse models Nature cancer High 35121889
2020 SETD6 methylates PAK4 specifically at lysine 473 (K473). K473 methylation activates β-catenin transcriptional activity, attenuates paxillin localization to focal adhesions, and reduces cell adhesion, migration, and invasion. In vitro methylation assay, site-directed mutagenesis (K473), β-catenin reporter assay, paxillin localization by immunofluorescence, adhesion/migration/invasion assay Scientific reports Medium 33051544
2021 CDK15 binds PAK4 and phosphorylates PAK4 at S291. Phosphorylation of PAK4 at S291 promotes CRC cell proliferation and anchorage-independent growth through β-catenin/c-Myc and MEK/ERK signaling pathways. PAK4 inhibition reverses the tumorigenic effects of CDK15 in CRC cells. Co-immunoprecipitation (CDK15-PAK4), in vitro/in cellulo kinase assay (S291 phosphorylation), site-directed mutagenesis, β-catenin/MEK-ERK pathway analysis, CDK15 KO mouse AOM/DSS model, CDX and PDX xenograft models Cell death and differentiation High 34262144
2010 PAK4 N-terminal domain interacts with ribonucleoprotein (RNP) complexes, and active PAK4 affects cap-independent (IRES-mediated) translation in vivo; the N-terminal domain contains sequences driving cytoplasmic localization and a nuclear export signal. Affinity chromatography of N-terminal domain, IRES-reporter assay in cells, nuclear/cytoplasmic fractionation Journal of cellular physiology Low 20578242
2018 Nuclear PAK4 (nPAK4) acts as a repressor of ERα-mediated transactivation in an E2-dependent manner; PAK4 binds ERα and co-translocates with it from the cytoplasm to the nucleus upon E2 stimulation, and promotes bone metastasis by targeting the LIFR (bone metastasis suppressor) locus. Co-immunoprecipitation (PAK4-ERα), nuclear fractionation upon E2 stimulation, ERα reporter assay, LIFR expression analysis, in vitro invasion assay, in vivo metastasis model Oncogene Medium 30177834

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 Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. The Journal of biological chemistry 221 11413130
2001 The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis. The Journal of biological chemistry 186 11278822
2008 Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling. Journal of cell science 164 18319301
2001 Activated PAK4 regulates cell adhesion and anchorage-independent growth. Molecular and cellular biology 153 11313478
2005 PAK4 mediates morphological changes through the regulation of GEF-H1. Journal of cell science 143 15827085
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 127 34368780
2016 Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. Molecular cancer therapeutics 126 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
2008 The pak4 protein kinase plays a key role in cell survival and tumorigenesis in athymic mice. Molecular cancer research : MCR 117 18644984
2020 Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma. Nature cancer 114 35121889
2002 PAK4 is activated via PI3K in HGF-stimulated epithelial cells. Journal of cell science 99 12244132
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
2014 PAK4 confers cisplatin resistance in gastric cancer cells via PI3K/Akt- and MEK/ERK-dependent pathways. Bioscience reports 84 27919028
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
2019 PAK4 signaling in health and disease: defining the PAK4-CREB axis. Experimental & molecular medicine 71 30755582
2005 Pak4 induces premature senescence via a pathway requiring p16INK4/p19ARF and mitogen-activated protein kinase signaling. Molecular and cellular biology 70 16227603
2009 Pak4, a novel Gab1 binding partner, modulates cell migration and invasion by the Met receptor. Molecular and cellular biology 69 19289496
2020 Exosome-mediated RNAi of PAK4 prolongs survival of pancreatic cancer mouse model after loco-regional treatment. Biomaterials 67 32977209
2017 MiR-145 inhibits human colorectal cancer cell migration and invasion via PAK4-dependent pathway. Cancer medicine 67 28440035
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 63 26598620
2017 Zic2 promotes tumor growth and metastasis via PAK4 in hepatocellular carcinoma. Cancer letters 59 28577975
2009 DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1. The international journal of biochemistry & cell biology 59 19778628
2015 An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nature communications 57 26607847
2016 PAK4 Methylation by SETD6 Promotes the Activation of the Wnt/β-Catenin Pathway. The Journal of biological chemistry 56 26841865
2011 Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma. Carcinogenesis 56 21325635
2010 The protein kinase Pak4 disrupts mammary acinar architecture and promotes mammary tumorigenesis. Oncogene 56 20697354
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
2021 CDK15 promotes colorectal cancer progression via phosphorylating PAK4 and regulating β-catenin/ MEK-ERK signaling pathway. Cell death and differentiation 53 34262144
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 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
2009 Essential role for the Pak4 protein kinase in extraembryonic tissue development and vessel formation. Mechanisms of development 45 19464366
2013 The Pak4 protein kinase is required for oncogenic transformation of MDA-MB-231 breast cancer cells. Oncogenesis 43 23732710
2012 PAK4 kinase activity and somatic mutation promote carcinoma cell motility and influence inhibitor sensitivity. Oncogene 41 22689056
2019 A novel PAK4-CEBPB-CLDN4 axis involving in breast cancer cell migration and invasion. Biochemical and biophysical research communications 39 30808546
2019 PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer. Nature communications 38 31399573
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
2011 PAK4 is required for regulation of the cell-cycle regulatory protein p21, and for control of cell-cycle progression. Journal of cellular biochemistry 38 21381077
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
2016 PAK4 Phosphorylates p53 at Serine 215 to Promote Liver Cancer Metastasis. Cancer research 37 27496712
2015 Glioblastomas require integrin αvβ3/PAK4 signaling to escape senescence. Cancer research 36 26297735
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
2014 p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines. Cancer research and treatment 33 25672581
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
2022 PAK4 in cancer development: Emerging player and therapeutic opportunities. Cancer letters 31 35798086
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
2015 The Cdc42 Effector Kinase PAK4 Localizes to Cell-Cell Junctions and Contributes to Establishing Cell Polarity. PloS one 30 26068882
2011 A key role for Pak4 in proliferation and differentiation of neural progenitor cells. Developmental biology 30 21382368
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
2020 Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis. BMC cancer 28 32041570
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
2019 PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer. Cancer letters 25 31121213
2019 PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors. Cancers 25 31795447
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
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
2022 Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells. Acta pharmaceutica Sinica. B 22 35755272
2021 A novel PAK4 inhibitor suppresses pancreatic cancer growth and enhances the inhibitory effect of gemcitabine. Translational oncology 22 34973571
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
2025 Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4. Communications biology 21 39833606
2021 The role of PAK4 in the immune system and its potential implication in cancer immunotherapy. Cellular immunology 21 34246086
2021 PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Molecular cancer therapeutics 21 34253597
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
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
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
2019 PAK4 Kinase Activity Plays a Crucial Role in the Podosome Ring of Myeloid Cells. Cell reports 18 31825823
2016 Study on the expression of PAK4 and P54 protein in breast cancer. World journal of surgical oncology 18 27297086
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
2017 LC-0882 targets PAK4 and inhibits PAK4-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells. American journal of translational research 16 28670365

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