Affinage

PAK6

Serine/threonine-protein kinase PAK 6 · UniProt Q9NQU5

Length
681 aa
Mass
74.9 kDa
Annotated
2026-06-10
49 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAK6 is a group II p21-activated serine/threonine kinase that couples Rho-family GTPase and steroid hormone receptor signaling to cytoskeletal dynamics, apoptosis, and gene expression (PMID:11773441, PMID:17292838). It binds GTP-loaded Cdc42 strongly and Rac weakly through its CRIB motif and is an effector of the atypical GTPases Chp/RhoV and RhoD, yet these GTPases do not stimulate its catalytic activity; instead PAK6 kinase activation is driven by direct, ligand-dependent binding to the androgen receptor (PMID:11773441, PMID:22339630, PMID:28486133, PMID:24130878). The catalytic domain adopts a group II PAK active conformation through rearrangement of helix αC, and the kinase is held in check by an N-terminal pseudosubstrate sequence whose disruption (melanoma-associated P52L) relieves autoinhibition (PMID:17292838, PMID:24204982). Through AR, PAK6 acts as a transcriptional corepressor and co-translocates to the nucleus with hormone, and it controls AR homeostasis by phosphorylating AR at Ser578 and Mdm2 at Thr158/Ser186 to promote AR ubiquitin-mediated degradation (PMID:11278661, PMID:23132866). PAK6 governs cell motility and cell-cell adhesion via multiple substrates: it phosphorylates LIMK1 (Thr508) to drive the cofilin/actin axis, phosphorylates β-catenin at cell-cell junctions in an IQGAP1- and E-cadherin-containing complex, and acts downstream of IQGAP3 to promote RhoA-dependent contractility and invadopodia (PMID:25714010, PMID:24352566, PMID:38763182). Its targeting to cell-cell adhesions requires the CRIB motif plus an adjacent polybasic region and depends on Cdc42 (PMID:26598554). In mitochondria, PAK6 phosphorylates ANT2 (Thr107) and destabilizes SIRT4 within a PAK6-SIRT4-ANT2 complex to suppress apoptosis, and it phosphorylates BAD at Ser112 to restrain the intrinsic death pathway (PMID:32194820, PMID:20054820). A neuronal axis links PAK6 to LRRK2: PAK6 phosphorylates 14-3-3γ at Ser59 to dissociate it from LRRK2, driving LRRK2 dephosphorylation, and localizes to the centrosome and cilium where it positively regulates ciliogenesis, with constitutively active PAK6 rescuing LRRK2 G2019S-associated defects (PMID:29311810, PMID:39419978). PAK6 also promotes ATR-CHK1-RAD51 homologous recombination repair, Wnt/β-catenin signaling via GSK3β, and MAPK14 (Ser56) phosphorylation in cancer cells (PMID:35902562, PMID:32782556, PMID:40194572). In vivo, Pak5/Pak6 double-knockout mice are viable but show locomotor and learning/memory deficits (PMID:18675265).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Established PAK6's first physiological partner by showing it binds the androgen receptor and represses its transcriptional output, defining PAK6 as a hormone receptor coregulator rather than a generic GTPase effector.

    Evidence Yeast two-hybrid, in vitro binding, co-localization, and reporter assays in mammalian cells

    PMID:11278661

    Open questions at the time
    • Did not identify the kinase substrate underlying repression
    • Mechanism of co-translocation not defined
  2. 2002 High

    Resolved the puzzle of how PAK6 is regulated by showing GTPases bind but do not activate it, while AR/ERα binding does, distinguishing PAK6 from canonical GTPase-activated PAKs.

    Evidence One-hybrid, GTPase binding assays, kinase activity, reporter assays, localization

    PMID:11773441

    Open questions at the time
    • Did not explain the structural basis of GTPase-independent activation
    • ERα substrate not identified
  3. 2007 High

    Defined the structural basis of the group II PAK active state, showing helix αC rearrangements that anchor the active conformation.

    Evidence High-resolution X-ray crystallography of group II PAK catalytic domains

    PMID:17292838

    Open questions at the time
    • Full-length regulatory architecture not captured
    • No GTPase or AR co-structure
  4. 2008 High

    Connected PAK6 to organism-level locomotor and cognitive function through genetics, and identified IQGAP1/PP1B as physical partners pointing toward cytoskeletal and adhesion roles.

    Evidence Pak5/Pak6 double-knockout mouse behavior; immunopurification-LC/MS/MS with reciprocal co-IP

    PMID:18642328 PMID:18675265

    Open questions at the time
    • Redundancy with PAK5 obscures PAK6-specific contribution
    • Behavioral phenotype not linked to a molecular substrate
  5. 2010 Medium

    Showed PAK6 is pro-survival by phosphorylating BAD at Ser112 to block intrinsic apoptosis, establishing a therapeutically relevant radiosensitization node.

    Evidence shRNA knockdown, clonogenic and apoptosis assays, phospho-BAD/Bcl-2 Western blots in prostate cancer cells

    PMID:20054820

    Open questions at the time
    • Direct kinase assay on BAD not shown
    • Single cell-type context
  6. 2012 High

    Defined the AR homeostasis mechanism: PAK6 phosphorylates AR (Ser578) and Mdm2 (Thr158/Ser186) to drive AR ubiquitin-mediated degradation, and established Chp/RhoV as a vesicular effector partner.

    Evidence In vitro kinase, mutagenesis, co-IP, ubiquitination, xenograft; yeast two-hybrid and co-IP for Chp

    PMID:22339630 PMID:23132866

    Open questions at the time
    • Functional output of Chp-PAK6 vesicular co-localization unresolved
    • How AR-bound PAK6 selects Mdm2 vs other substrates not defined
  7. 2013 High

    Established PAK6 substrate specificity, pseudosubstrate autoinhibition, and an oncogenic activating mutation, while defining AR-stimulated kinase activation as a driver of motility and β-catenin as a junctional substrate within an IQGAP1/E-cadherin complex.

    Evidence Peptide profiling, kinase assays, P52L mutagenesis, co-crystal structures; co-IP, junction localization, colony escape assays; AR siRNA and PAK6 mutant motility assays

    PMID:24130878 PMID:24204982 PMID:24352566

    Open questions at the time
    • Physiological relevance of PACSIN1 phosphorylation untested in vivo
    • Direct β-catenin phosphosite not mapped
  8. 2015 Medium

    Mapped the cytoskeletal effector arm by showing PAK6 phosphorylates LIMK1 (Thr508) to engage cofilin and actin dynamics, and defined the CRIB-plus-polybasic, Cdc42-dependent targeting to cell-cell adhesions required for kinase-dependent colony escape.

    Evidence Co-IP, phospho-LIMK1/cofilin blots, orthotopic mouse model; domain mutagenesis and Cdc42 knockdown with colony escape assay

    PMID:25714010 PMID:26598554

    Open questions at the time
    • Direct LIMK1 kinase assay limited
    • How Cdc42 promotes localization without activating kinase unresolved
  9. 2017 High

    Linked PAK6 to Parkinson's-relevant LRRK2 biology by showing 14-3-3γ Ser59 phosphorylation dissociates LRRK2 and drives its dephosphorylation, with rescue of G2019S neurite defects; RhoD was placed upstream as a plasma-membrane recruiter antagonizing RhoC-ROCK.

    Evidence Co-IP interactome, in vitro kinase assay, neurite rescue; genetic epistasis with RhoD/RhoC and viral F11

    PMID:28486133 PMID:29311810

    Open questions at the time
    • Endogenous PAK6 activation cue at the membrane not defined
    • Whether 14-3-3γ phosphorylation occurs in disease tissue untested
  10. 2018 Medium

    Showed PAK6 is itself epigenetically controlled, repressed by a DNMT1-EZH2/PRC2 H3K27me3 mechanism that limits cortical interneuron morphological complexity.

    Evidence ChIP at the PAK6 locus, EZH2 inhibition, DNMT1 and PAK6 knockdown with morphological rescue

    PMID:29912614

    Open questions at the time
    • Direct DNMT1 recruitment to the PAK6 locus not shown
    • Downstream PAK6 substrates in interneurons unidentified
  11. 2020 High

    Defined a mitochondrial pro-survival module: PAK6 localizes to the inner membrane, phosphorylates ANT2 (Thr107), and destabilizes SIRT4 to suppress apoptosis, with pharmacological PAK6 inhibition shown to sensitize drug-resistant cancer cells via RAS/MAPK and mitochondrial effects.

    Evidence Immuno-EM localization, co-IP, ubiquitination, K105/T107 mutagenesis, apoptosis, xenograft; PAK6 inhibitor with pathway and mitochondrial readouts in CML

    PMID:32194820 PMID:32270193

    Open questions at the time
    • How a kinase reaches the inner membrane mechanistically unclear
    • RAS/MAPK linkage in CML not mechanistically dissected
  12. 2022 Medium

    Expanded PAK6 into nuclear DNA repair, Wnt signaling, and PP2A regulation: it promotes ATR-CHK1-RAD51 homologous recombination, activates Wnt/β-catenin via GSK3β, and phosphorylates PPP2R2C (Ser381) to modulate its LRRK2 binding while leaving the dominant 14-3-3γ LRRK2 mechanism intact.

    Evidence Nuclear fractionation, RAD51 foci, ATR inhibitor epistasis; co-IP and Wnt pathway blots; PhosTag in vitro kinase with purified PPP2R2C and S381A mutant

    PMID:32782556 PMID:35016853 PMID:35902562

    Open questions at the time
    • Direct nuclear substrate driving ATR activation not identified
    • Whether GSK3β is a direct PAK6 substrate not shown
  13. 2024 High

    Established PAK6 at the centrosome/cilium as a positive regulator of ciliogenesis and refined the LRRK2 interface, showing PD mutations in the Roc-COR region reduce PAK6-LRRK2 affinity and that active PAK6 rescues G2019S but not R1441C defects.

    Evidence Endogenous localization, ciliogenesis assays across cell types, active-PAK6 rescue, microscale thermophoresis and AlphaFold2 modeling; reconstituted PPP2R2C kinase assay

    PMID:38169846 PMID:39419978

    Open questions at the time
    • Ciliary substrate of PAK6 not identified
    • Mechanism distinguishing G2019S vs R1441C rescue at the molecular level incomplete
  14. 2025 Medium

    Detailed post-transcriptional and cell-cycle control of PAK6 oncogenic function across cancers: METTL3/IGF2BP1 m6A, HNRNPC-lactylation-driven oncogenic isoform splicing, and PUM1-mediated mRNA stabilization upregulate PAK6, while PAK6 phosphorylates MAPK14 (Ser56) and acts through MDM2-p21 and ferroptosis pathways.

    Evidence Kinase assays (MAPK14 Ser56, NeuO probe), m6A/RIP/lactylation proteomics, splicing analysis, PAK6 knockdown/inhibition with senescence and ferroptosis readouts, xenografts

    PMID:40194572 PMID:40650306 PMID:40694989 PMID:40734467 PMID:41435694

    Open questions at the time
    • Whether MDM2-p21 effects require direct MDM2 phosphorylation not fully shown
    • PUM1-ferroptosis link rests on a single low-confidence study
    • Isoform-specific activities not biochemically separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GTPase-binding kinase that is not activated by its GTPases integrates AR, LRRK2, mitochondrial, ciliary, and DNA-repair signaling into context-specific outputs remains unresolved.
  • No unifying model of how upstream cues select among PAK6 substrate sets
  • Endogenous activation mechanism in neurons vs epithelia undefined
  • No full-length structure showing pseudosubstrate-to-active transition

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:0140110 transcription regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1852241 Organelle biogenesis and maintenance 1 R-HSA-73894 DNA Repair 1
Partners
ARCDC42GSK3BIQGAP1LIMK1LRRK2MDM2SIRT4
Complex memberships
PAK6-IQGAP1-E-cadherin complexPAK6-SIRT4-ANT2 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PAK6 physically interacts with the androgen receptor (AR) in a domain-specific and ligand-dependent manner; PAK6 co-translocates into the nucleus with AR in response to androgen; PAK6 represses AR-mediated transcription in transient transfection assays. Yeast two-hybrid, in vitro binding, immunofluorescence co-localization, transient transfection reporter assay The Journal of biological chemistry High 11278661
2002 PAK6 binds strongly to GTP-bound Cdc42 and weakly to GTP-Rac via its CRIB domain; PAK6 kinase activity is not stimulated by Cdc42 or Rac but can be stimulated by AR binding; PAK6 also binds ERα with binding enhanced by 4-hydroxytamoxifen; PAK6 inhibits both AR and ERα transcriptional activity; epitope-tagged PAK6 is primarily cytoplasmic. Mammalian one-hybrid assay, in vitro binding, GTPase binding assays, transient transfection reporter assay, immunofluorescence localization Molecular endocrinology High 11773441
2007 Crystal structures of active, monophosphorylated PAK6 catalytic domain reveal group II PAK structural plasticity including rearrangements of helix αC forming an additional helical turn at αC N-terminus and a distortion of its C-terminus, forming interactions that link the glycine-rich loop, αC, and the activation segment to anchor αC in an active conformation. X-ray crystallography (multiple high-resolution structures of PAK4, PAK5, PAK6 catalytic domains; inhibitor co-crystal structures) Structure High 17292838
2008 Pak5/Pak6 double-knockout mice are viable and fertile but exhibit locomotor deficits and learning and memory impairments, establishing that PAK6 together with PAK5 is required for normal locomotion and cognitive function in vivo. Gene knockout (mouse), behavioral assays (locomotion, learning and memory) Developmental biology High 18675265
2008 PAK6 co-immunoprecipitates with IQGAP1 and protein phosphatase 1B (PP1B) in prostate cancer cells, identifying these as PAK6 interacting proteins. Immunopurification of 3xFlag-tagged PAK6 followed by LC/MS/MS, confirmed by co-immunoprecipitation The Prostate Medium 18642328
2010 PAK6 inhibition reduces phosphorylation of BAD at Ser112, leading to increased BAD binding to Bcl-2 and Bcl-XL, cytochrome c release, caspase activation, and apoptosis; PAK6 knockdown also increases radiosensitivity of prostate cancer cells. shRNA stable knockdown, clonogenic survival assay, apoptosis assay (flow cytometry), Western blot (BAD phosphorylation, Bcl-2 binding, cleaved caspase-3) The Prostate Medium 20054820
2012 PAK6 phosphorylates AR at Ser-578, promoting AR association with E3 ligase Mdm2 and AR ubiquitin-mediated degradation; PAK6 also phosphorylates Mdm2 at Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation; PAK6 co-localizes with AR in the cytoplasm of normal prostate epithelium. In vitro kinase assay, immunofluorescence co-localization, co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, in vivo xenograft The Journal of biological chemistry High 23132866
2012 PAK6 is a novel effector of the atypical Rho GTPase Chp/RhoV; interaction depends on the activation state of Chp and involves the effector domain of Chp and the CRIB motif of PAK6; Chp does not activate PAK6 (no change in S560 phosphorylation); in NCI-H1299 cells, Chp co-localizes with PAK6 on vesicular structures in an activation state-dependent manner. Yeast two-hybrid, co-immunoprecipitation, point mutagenesis of effector domain and CRIB motif, immunofluorescence co-localization Biochemistry (Biokhimiia) Medium 22339630
2013 PAK6 localizes to cell-cell junctions and directly interacts with IQGAP1 via its kinase domain; PAK6 forms a complex with E-cadherin and IQGAP1 downstream of HGF signaling; β-catenin is a novel PAK6 substrate at cell-cell junctions; PAK6/IQGAP1 complex drives epithelial colony escape and cell-cell dissociation. Co-immunoprecipitation, immunofluorescence localization, kinase domain binding assay, co-expression overexpression/depletion assays, cell colony escape assay Cellular and molecular life sciences Medium 24352566
2013 PAK6 has a peptide substrate specificity similar to PAK4 and PAK5; PAK6 is autoinhibited by an N-terminal pseudosubstrate peptide; a melanoma-associated P52L mutation in the pseudosubstrate reduces autoinhibition and increases phosphorylation of PACSIN1 (Syndapin I) in cells; co-crystal structures of PAK6 catalytic domain with PF-3758309 (1.4 Å) and sunitinib (1.95 Å) determined. Peptide library substrate profiling, in vitro kinase assay, pseudosubstrate peptide inhibition assay, site-directed mutagenesis (P52L), cellular phosphorylation assay, X-ray crystallography PloS one High 24204982
2013 PAK6 kinase activation is stimulated by direct AR interaction in response to androgen; siRNA knockdown of AR reduces androgen-stimulated PAK6 kinase activation; a non-AR-interacting PAK6 mutant shows dampened kinase activation and fails to promote androgen-stimulated cell motility and invasion. In vitro kinase assay, siRNA knockdown, cell motility and invasion assay, mutant PAK6 expression PloS one Medium 24130878
2015 PAK6 targeting to cell-cell adhesions requires both its CRIB domain and an adjacent polybasic region in the N-terminus; Cdc42 knockdown inhibits PAK6 localization to cell-cell adhesions; PAK6-driven epithelial colony escape requires kinase activity and is abolished by mutations disrupting cell-cell adhesion targeting. Deletion/point mutagenesis, siRNA knockdown of Cdc42, immunofluorescence localization, colony escape assay Journal of cell science Medium 26598554
2015 PAK6 phosphorylates LIMK1 at Thr-508, activating it; activated LIMK1 phosphorylates cofilin, promoting stress fiber and actin filament formation required for cell motility and invasion; PAK6 and LIMK1 co-localize in the cytoplasm. Co-immunoprecipitation, immunofluorescence co-localization, Western blot (phospho-LIMK1, phospho-cofilin), in vivo orthotopic mouse model Oncotarget Medium 25714010
2017 PAK6 phosphorylates 14-3-3γ at Ser59; this phosphorylation dissociates 14-3-3γ from client proteins including LRRK2, causing LRRK2 dephosphorylation at Ser935; constitutively active PAK6 rescues G2019S LRRK2-associated neurite shortening through 14-3-3γ phosphorylation. Co-immunoprecipitation (PAK6 interactome), in vitro kinase assay (phosphorylation of 14-3-3γ at Ser59), co-IP (14-3-3γ/LRRK2 dissociation), immunofluorescence (neurite length assay), constitutively active PAK6 rescue experiment Frontiers in molecular neuroscience High 29311810
2017 RhoD recruits PAK6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing; vaccinia virus protein F11 inhibits RhoD signaling, preventing RhoD from activating PAK6, thereby releasing suppression of RhoC-ROCK-mediated cell contraction. Genetic epistasis (RhoD, PAK6, RhoC knockdown/overexpression), immunofluorescence localization, cell contraction and blebbing assays Developmental cell Medium 28486133
2018 DNMT1 represses PAK6 transcription by interacting with EZH2 (PRC2 core enzyme) to mediate repressive H3K27 trimethylation at PAK6 gene regulatory regions; inhibition of EZH2 elevates PAK6 expression and increases morphological complexity in cortical interneurons, rescued by PAK6 siRNA knockdown. ChIP (H3K4me3, H3K27me3 at PAK6 locus), EZH2 inhibition, DNMT1 knockdown, siRNA-mediated PAK6 knockdown, morphological analysis Epigenetics Medium 29912614
2020 PAK6 is mainly located in the mitochondrial inner membrane; PAK6 promotes SIRT4 ubiquitin-mediated proteolysis; SIRT4 deacetylates ANT2 at K105 to promote ANT2 ubiquitination degradation; PAK6 directly phosphorylates ANT2 at T107 to inhibit apoptosis of prostate cancer cells; the PAK6-SIRT4-ANT2 complex regulates mitochondrial apoptosis. Immunofluorescence, immunoelectron microscopy (subcellular localization), co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K105, T107), flow cytometry (apoptosis), xenograft model Theranostics High 32194820
2020 Pharmacological inhibition of PAK6 perturbs the RAS/MAPK pathway and mitochondrial activity in CML drug-resistant cells, sensitizing them to TKI therapy. PAK6 pharmacological inhibition, pathway analysis (RAS/MAPK), mitochondrial activity assay, xenotransplantation model Blood Medium 32270193
2022 PAK6 moves into the nucleus to promote ATR activation, which activates CHK1 and recruits RAD51 from cytoplasm to DNA damage sites to enable homologous recombination repair; ATR inhibitor (AZD6738) blocks PAK6-mediated HR repair, reversing oxaliplatin resistance. PAK6 knockdown/overexpression, ATR inhibitor treatment, HR repair assay (RAD51 foci), Western blot (ATR/CHK1 activation), nuclear fractionation Cell death & disease Medium 35902562
2022 PAK6 interacts with GSK3β (confirmed by co-IP and fluorescence co-localization) and activates the Wnt/β-catenin signaling pathway, leading to GSK3β phosphorylation, increased Cyclin D1, and decreased β-catenin phosphorylation and E-cadherin. Co-immunoprecipitation, fluorescence co-localization, shRNA knockdown and overexpression, Western blot (Wnt/β-catenin pathway components) Oncology letters Medium 32782556
2022 PAK6 phosphorylates the PP2A regulatory subunit PPP2R2C at Ser381; this phosphorylation alters PPP2R2C binding to LRRK2 and changes PPP2R2C subcellular localization in a phosphorylation-dependent manner; however, LRRK2 dephosphorylation by PAK6 is unaffected by PPP2R2C S381 phosphorylation, indicating the 14-3-3γ phosphorylation mechanism is dominant. PhosTag gel electrophoresis with purified proteins (in vitro kinase assay), co-immunoprecipitation, subcellular localization imaging, site-directed mutagenesis (S381A phosphodead) Brain research Medium 35016853
2023 PAK6 phosphorylates the PP2A regulatory subunit PPP2R2C at S381 (confirmed with purified proteins); S381 phosphorylation does not affect PP2A holoenzyme formation but a S381A phosphodead mutant shows impaired binding to LRRK2; PAK6 kinase activity changes PPP2R2C subcellular localization in a S381-dependent manner. In vitro kinase assay (PhosTag gel, purified proteins), co-immunoprecipitation, subcellular localization, site-directed mutagenesis Frontiers in molecular neuroscience Medium 38169846
2024 PAK6 localizes at the centrosome and cilium; PAK6 positively regulates ciliogenesis in tumor cells, neurons, and astrocytes; constitutively active PAK6 rescues ciliogenesis and centrosomal cohesion defects caused by LRRK2 G2019S but not R1441C mutation; PD mutations in LRRK2 affecting Roc-COR structure (including R1441C) substantially decrease PAK6 affinity for LRRK2 (measured by microscale thermophoresis and AlphaFold2 modeling). Protein-protein interaction arrays, immunofluorescence (endogenous PAK6 at centrosome/cilium), ciliogenesis assay (multiple cell types), constitutively active PAK6 rescue, microscale thermophoresis (binding affinity), AlphaFold2 computational modeling Cell death & disease High 39419978
2024 PAK6 acts downstream of IQGAP3 to promote RhoA-dependent actomyosin contractility, cell migration, and invadopodia formation in triple-negative breast cancer cells; PAK6 depletion phenocopies IQGAP3 depletion and PAK6 overexpression rescues IQGAP3 depletion phenotype. Co-immunoprecipitation (IQGAP3-PAK6 interaction), siRNA knockdown, overexpression rescue, RhoA activity assay, cell migration assay, invadopodia assay Cellular signalling Medium 38763182
2025 PAK6 phosphorylates MDM2, and PAK6 inhibition in TKI-resistant CML cells induces G2-M cell cycle arrest and cellular senescence through a PAK6-MDM2-p21 axis. Lentiviral PAK6 knockdown, pharmacological PAK6 inhibition, cell cycle analysis, senescence assays, Western blot (MDM2, p21) International journal of molecular sciences Medium 40650306
2025 PAK6 phosphorylates MAPK14 at Ser56, promoting proliferation, migration, and invasion of cervical cancer cells; METTL3-mediated m6A modification of PAK6 mRNA stabilizes it through the m6A reader IGF2BP1, increasing PAK6 protein levels. In vitro and cellular kinase assay (PAK6 phosphorylates MAPK14 at Ser56), gain/loss-of-function studies, m6A methylation assay, m6A reader pulldown, in vivo xenograft International journal of biological macromolecules Medium 40194572
2025 NeuO probe undergoes phosphorylation by PAK6 kinase, resulting in structural changes that cause high fluorescence and intracellular retention in neurons (fluorogenic activation). In vitro kinase assay (PAK6 phosphorylates NeuO probe), fluorescence measurement, neuronal selectivity assay Angewandte Chemie Medium 40734467
2025 HNRNPC lactylation at K176 strengthens binding to poly-U motifs in PAK6 pre-mRNA, facilitating expression of an oncogenic PAK6 isoform (PAK6S) through alternative splicing in pancreatic cancer. Lactylation proteomics, RNA immunoprecipitation (HNRNPC binding to PAK6 pre-mRNA), alternative splicing analysis, gain/loss-of-function studies Cancer letters Medium 41435694
2025 PUM1 binds PAK6 mRNA and stabilizes it, contributing to ferroptosis resistance in lung adenocarcinoma cells; PAK6 silencing elevates Fe2+ and MDA levels and enhances Erastin-induced ferroptosis. RNA immunoprecipitation (PUM1-PAK6 mRNA binding), luciferase assay, siRNA knockdown, ferroptosis markers (Fe2+, MDA), in vivo xenograft Pathology, research and practice Low 40694989

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6. The Journal of biological chemistry 132 11278661
2022 Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis. Molecular cancer 118 35255921
2002 AR and ER interaction with a p21-activated kinase (PAK6). Molecular endocrinology (Baltimore, Md.) 114 11773441
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
2008 Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion. Developmental biology 72 18675265
2015 Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway. Oncotarget 67 25714010
2008 Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins. The Prostate 63 18642328
2012 p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2). The Journal of biological chemistry 51 23132866
2020 Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex. Theranostics 48 32194820
2010 Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of prostate cancer cells. The Prostate 48 20054820
2017 PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2. Frontiers in molecular neuroscience 46 29311810
2020 The miR-185/PAK6 axis predicts therapy response and regulates survival of drug-resistant leukemic stem cells in CML. Blood 41 32270193
2022 SLC6A14 facilitates epithelial cell ferroptosis via the C/EBPβ-PAK6 axis in ulcerative colitis. Cellular and molecular life sciences : CMLS 36 36272033
2018 DNMT1 modulates interneuron morphology by regulating Pak6 expression through crosstalk with histone modifications. Epigenetics 34 29912614
2013 A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions. Cellular and molecular life sciences : CMLS 32 24352566
2022 PAK6 promotes homologous-recombination to enhance chemoresistance to oxaliplatin through ATR/CHK1 signaling in gastric cancer. Cell death & disease 30 35902562
2015 MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling. Oncology reports 30 26058485
2017 RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6. Developmental cell 27 28486133
2016 Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells. Oncotarget 25 27542207
2015 PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape. Journal of cell science 24 26598554
2013 Functional deficits in PAK5, PAK6 and PAK5/PAK6 knockout mice. PloS one 23 23593460
2012 Pak6 protein kinase is a novel effector of an atypical Rho family GTPase Chp/RhoV. Biochemistry. Biokhimiia 22 22339630
2020 PAK6 promotes cervical cancer progression through activation of the Wnt/β-catenin signaling pathway. Oncology letters 21 32782556
2013 Substrate and inhibitor specificity of the type II p21-activated kinase, PAK6. PloS one 21 24204982
2013 Direct interaction between AR and PAK6 in androgen-stimulated PAK6 activation. PloS one 19 24130878
2023 Urinary exosome proteins PAK6 and EGFR as noninvasive diagnostic biomarkers of diabetic nephropathy. BMC nephrology 12 37789280
2020 miR-27a promotion resulting from silencing of HDAC3 facilitates the recovery of spinal cord injury by inhibiting PAK6 expression in rats. Life sciences 12 32679145
2024 PAK6 acts downstream of IQGAP3 to promote contractility in triple negative breast cancer cells. Cellular signalling 8 38763182
2022 The Roc domain of LRRK2 as a hub for protein-protein interactions: a focus on PAK6 and its impact on RAB phosphorylation. Brain research 8 35016853
2022 Circular RNA circ_0001006 aggravates cardiac hypertrophy via miR-214-3p/PAK6 axis. Aging 8 35306484
2014 Predictive value of PAK6 and PSMB4 expression in patients with localized prostate cancer treated with dose-escalation radiation therapy and androgen deprivation therapy. Urologic oncology 8 24946957
2013 Differential sensitivity of Pak5, Pak6, and Pak5/Pak6 double-knockout mice to the stimulant effects of amphetamine and exercise-induced alterations in body weight. Nutritional neuroscience 7 23710594
2025 METTL3-mediated m6A modification of PAK6 drives cervical cancer progression through activating MAPK14. International journal of biological macromolecules 6 40194572
2022 The role of the miR-4306/PAK6 axis in degenerative nucleus pulposus cells in human intervertebral disc degeneration. Cellular signalling 6 36423859
2024 Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson's Disease. Journal of Parkinson's disease 5 38640169
2011 Expression and role of PAK6 after spinal cord injury in adult rat. Chinese journal of traumatology = Zhonghua chuang shang za zhi 5 22118481
2024 Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells. Journal of cellular and molecular medicine 4 39233332
2024 miR-3191 promotes the proliferation and metastasis of hepatocellular carcinoma via regulating PAK6. Infectious agents and cancer 4 39696440
2023 PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation. Frontiers in molecular neuroscience 4 38169846
2022 Differential roles and regulation of the protein kinases PAK4, PAK5 and PAK6 in melanoma cells. The Biochemical journal 4 35969127
2025 Identification of a PAK6-Mediated MDM2/p21 Axis That Modulates Survival and Cell Cycle Control of Drug-Resistant Stem/Progenitor Cells in Chronic Myeloid Leukemia. International journal of molecular sciences 3 40650306
2024 PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner. Cell death & disease 3 39419978
2019 Detection of the steroid receptor interacting protein, PAK6, in a neuronal cell line. Heliyon 2 30923762
2026 CCL2 and PAK6 as Candidate Biomarkers of Neuroinflammation in Parkinson's Disease: An Integrated Machine Learning and Single-Nucleus Transcriptomic Study. Brain sciences 0 42192776
2025 PUM1 enhances PAK6 mRNA stability and contributes to growth and ferroptosis resistance in lung adenocarcinoma cells. Pathology, research and practice 0 40694989
2025 Unraveling the Mode of Action of a Neuron-Specific Fluorescent Probe, NeuO: Intracellular Phosphorylation Through PAK6 Kinase. Angewandte Chemie (International ed. in English) 0 40734467
2025 PAK6 drives tumor microenvironment remodeling in nasopharyngeal carcinoma with lymph node necrosis: implications for distant metastasis and survival. International immunopharmacology 0 41101234
2025 HNRNPC lactylation promotes pancreatic cancer progression through mediating the alternative splicing of PAK6. Cancer letters 0 41435694
2007 [Cloning of human PAK6 cDNA, preparation of anti-PAK6 polyclonal antibody and PAK6 expression in prostate cancer]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 17584649

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