Affinage

PAK5

Serine/threonine-protein kinase PAK 6 · UniProt Q9NQU5

Length
681 aa
Mass
74.9 kDa
Annotated
2026-06-10
61 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAK5 (PAK7) is a constitutively active, brain-enriched group II PAK serine/threonine kinase that functions as an effector of Rho-family GTPases in cytoskeletal remodeling, neuronal development, mitochondrial regulation, and apoptotic control, and is co-opted in cancer to drive proliferation and metastasis (PMID:11756552, PMID:12897128). It binds Cdc42 in a GTP-dependent manner through its CRIB motif, yet unlike group I PAKs its high kinase activity is independent of GTPase binding; this autonomy is maintained by a central oligomerization domain that interferes with autoinhibitory domain engagement of the catalytic domain (PMID:12032833, PMID:27095851). PAK5 carries N-terminal targeting signals (a mitochondrial targeting sequence, an NES, and an NLS) that direct constitutive mitochondrial localization and regulated shuttling to the nucleus (PMID:16581795). At the mitochondrion it is anti-apoptotic, phosphorylating BAD on Ser112 to block its mitochondrial localization and phosphorylating AIF on Thr281 to prevent AIF/importin-α3 complex formation and nuclear translocation (PMID:12897128, PMID:33867848). In neurons, PAK5 promotes filopodia formation and neurite outgrowth downstream of Cdc42/Rac and antagonistic to RhoA, stabilizes microtubules by directly binding and suppressing MARK2 kinase activity toward tau, phosphorylates the synaptic vesicle proteins Pacsin1 and Synaptojanin1 to promote their interaction, and—downstream of AKT—phosphorylates the mitochondrial anchor syntaphilin to remobilize damaged axonal mitochondria after ischemic injury (PMID:11756552, PMID:16014608, PMID:22371566, PMID:34087103). PAK5/PAK6 double-knockout mice show locomotor and learning/memory deficits, whereas single PAK5 knockouts are grossly normal, indicating functional redundancy among group II PAKs in vivo (PMID:14517284, PMID:18675265). In cancer, PAK5 phosphorylates a broad set of transcription factors and metabolic and RNA-processing enzymes—including E47 (Ser39), GATA1 (Ser161/Ser187), SATB1 (Ser47), Slug (Ser87), NF-κB p65, DDX5 (Thr69), DNPEP (Ser119), PKM2 (Ser519), METTL14 (Ser399), and HMGCS2—to drive EMT, metastasis, glycolysis, and treatment resistance (PMID:25726523, PMID:26212009, PMID:30082769, PMID:34936874, PMID:39331255, PMID:40258843, PMID:41834498).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 Medium

    Established PAK5 as a Rho-GTPase effector controlling neuronal morphology, placing it downstream of Cdc42/Rac and antagonistic to RhoA in neurite development.

    Evidence Dominant-negative and constitutively active mutants in N1E-115 neuroblastoma cells with epistasis against activated RhoA and dominant-negative JNK; GTP-dependent CRIB binding assays

    PMID:11756552 PMID:12032833

    Open questions at the time
    • Endogenous substrates driving neurite outgrowth not identified
    • How kinase activity is engaged independent of GTPase binding unresolved at this stage
  2. 2003 High

    Defined PAK5 as a constitutively active, mitochondrially localized anti-apoptotic kinase, identifying BAD Ser112 as a direct substrate and decoupling activity from Cdc42/Rac.

    Evidence Subcellular fractionation, in vitro kinase assay, site-directed mutagenesis, and apoptosis assays with camptothecin/C2-ceramide

    PMID:12897128

    Open questions at the time
    • Mechanism keeping kinase constitutively active not defined
    • Other mitochondrial substrates unknown
  3. 2003 High

    Tested PAK5's in vivo requirement, revealing functional redundancy among Rho-GTPase targets since single-knockout mice are normal.

    Evidence Targeted gene disruption in mice with histological and behavioral analysis

    PMID:14517284

    Open questions at the time
    • Redundant partners not identified in this study
    • Subtle phenotypes not probed
  4. 2005 High

    Showed PAK5 stabilizes microtubules through a non-catalytic mechanism by directly binding MARK2 and suppressing its kinase activity toward tau, while reshaping the actin cytoskeleton.

    Evidence Co-IP, in vitro kinase inhibition, deletion mapping, and cytoskeletal phenotyping in CHO cells

    PMID:16014608

    Open questions at the time
    • Structural basis of catalytic-domain interaction not resolved
    • Physiological relevance in neurons not directly tested
  5. 2006 High

    Mapped the N-terminal targeting code (MTS/NES/NLS) and linked mitochondrial localization to anti-apoptotic function, establishing regulated mitochondria-to-nucleus shuttling.

    Evidence Deletion mutagenesis, leptomycin B export blockade, fractionation, and knockdown/rescue apoptosis assays; additional Rho GTPase (RhoD/RhoH) interaction analysis

    PMID:16581795 PMID:17064668

    Open questions at the time
    • Signals triggering nuclear import not defined
    • Nuclear substrates not yet identified
  6. 2007 High

    Provided atomic-resolution structures of the active group II PAK catalytic domain, defining the active αC conformation and enabling inhibitor co-crystallization.

    Evidence X-ray crystallography of PAK4/5/6 catalytic domains with a tri-substituted purine inhibitor

    PMID:17292838

    Open questions at the time
    • Full-length autoregulatory architecture not captured
    • Oligomerization-based activation not addressed structurally
  7. 2008 High

    Demonstrated that PAK5 and PAK6 jointly support locomotion and cognition, resolving the single-knockout redundancy as compensation among group II PAKs.

    Evidence PAK5/PAK6 double-knockout mice with behavioral testing for locomotion and learning/memory

    PMID:18675265

    Open questions at the time
    • Cellular/molecular substrates underlying behavioral deficits not identified
    • Region-specific contributions unresolved
  8. 2012 High

    Identified Pacsin1 and Synaptojanin1 as brain substrates via unbiased chemical-genetic labeling, linking PAK5 to synaptic vesicle endocytosis.

    Evidence Analog-sensitive kinase substrate labeling in brain extract, in vitro kinase assay, and in vitro/in vivo co-IP

    PMID:22371566

    Open questions at the time
    • Phosphosites on the substrates not pinpointed
    • In vivo consequence for vesicle recycling not directly measured
  9. 2016 Medium

    Explained the molecular basis of PAK5's constitutive activity, showing a central oligomerization domain drives dimerization that blocks autoinhibitory domain engagement.

    Evidence Gel filtration, deletion analysis, in vitro kinase assay, and AID domain swapping comparing PAK4 (monomeric/inactive) and PAK5 (dimeric/active)

    PMID:27095851

    Open questions at the time
    • Structure of the oligomerization interface not solved
    • Whether oligomerization is regulated in cells unknown
  10. 2021 High

    Established PAK5 as an injury-responsive axonal kinase that remobilizes damaged mitochondria by phosphorylating syntaphilin downstream of AKT.

    Evidence Neuronal injury/ischemia models, in vivo brain injury models, SNPH phosphorylation assay, mitochondrial trafficking imaging, and AKT epistasis

    PMID:34087103

    Open questions at the time
    • SNPH phosphosite not specified here
    • How injury signals activate PAK5 synthesis spatially not fully resolved
  11. 2021 Medium

    Extended the mitochondrial anti-apoptotic program by showing PAK5 phosphorylates AIF (Thr281) to block its importin-α3-dependent nuclear translocation.

    Evidence Phosphorylation assay, AIF/importin-α3 co-IP, mitochondrial membrane potential/permeability assays, and breast cancer models

    PMID:33867848

    Open questions at the time
    • Single lab; reciprocal validation of complex disruption limited
    • Relative contribution versus BAD pathway unquantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PAK5 selects among its large and growing roster of cancer-associated substrates in specific tissue and signaling contexts, and how its mitochondrial/nuclear shuttling is dynamically directed in vivo, remains unresolved.
  • No unifying model for substrate selectivity across tissues
  • Upstream cues governing nuclear translocation in cancer not defined
  • Many cancer substrate findings rest on single-lab Co-IP/phosphorylation studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 5 GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 4 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 7 R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3
Partners
CDC42DDX5DNPEPGATA1GSK3BITGB1MARK2YWHAZ

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PAK5 is a novel target of Rho GTPases Cdc42 and Rac; it promotes filopodia induction and neurite outgrowth in N1E-115 neuroblastoma cells in a kinase activity-dependent manner. Dominant-negative PAK5 inhibited neurite outgrowth, and activated RhoA abolished PAK5-induced neurite formation, placing PAK5 downstream of Cdc42/Rac and antagonistic to Rho in the neurite development pathway. PAK5 also activates the JNK pathway, but dominant-negative JNK did not block neurite outgrowth. Dominant-negative and constitutively active mutant expression in N1E-115 cells; morphological assays; epistasis with dominant-negative JNK and activated RhoA Molecular and cellular biology Medium 11756552
2002 PAK5 preferentially binds Cdc42 in a GTP-dependent manner via its CRIB motif, but unlike PAK-I family kinases, its kinase activity does not require Cdc42 binding. Overexpression of PAK5 activates JNK but not p38 or ERK pathways. GTP-dependent binding assay; CRIB mutant analysis; MAPK pathway activation assays Oncogene Medium 12032833
2003 PAK5 is constitutively localized to mitochondria (independent of kinase activity or Cdc42 binding), has constitutively high kinase activity not regulated by Cdc42/Rac, prevents apoptosis induced by camptothecin and C2-ceramide by phosphorylating BAD on Ser-112 in a PKA-independent manner, and prevents BAD localization to mitochondria. Subcellular fractionation; in vitro kinase assay; site-directed mutagenesis; apoptosis assays with camptothecin and C2-ceramide; BAD phosphorylation analysis Molecular and cellular biology High 12897128
2003 PAK5 knockout mice develop normally and are fertile, with no apparent nervous system abnormalities, suggesting functional redundancy between PAK5 and other Rho GTPase targets in vivo. Targeted gene disruption (knockout mice); histological and behavioral analysis Molecular and cellular biology High 14517284
2005 PAK5 directly binds MARK2 via their catalytic domains and suppresses MARK2 kinase activity toward tau protein without requiring phosphorylation. In transfected CHO cells, PAK5 and MARK2 co-localize on endosomes containing AP-1/2. PAK5 keeps microtubules stable by downregulating MARK2 while simultaneously destabilizing F-actin (eliminating stress fibers and focal adhesions) and inducing filopodia. Co-immunoprecipitation; in vitro kinase assay; deletion/mutagenesis analysis; subcellular fractionation and co-localization in CHO cells; cytoskeletal phenotyping Molecular biology of the cell High 16014608
2006 PAK5 contains three N-terminal regulatory sequences: a mitochondrial targeting sequence, a nuclear export sequence (NES), and a nuclear localization sequence (NLS). PAK5 shuttles between mitochondria and nucleus; blockade of nuclear export with leptomycin B causes endogenous PAK5 to accumulate in the nucleus. Mitochondrial localization of PAK5 is required for its anti-apoptotic function; a PAK5 mutant unable to localize to mitochondria fails to protect cells from apoptosis. Reduction of endogenous PAK5 in neuroblastoma and neural stem cells increases apoptosis sensitivity. Deletion mutagenesis of targeting sequences; leptomycin B nuclear export blockade; live-cell imaging and fractionation; apoptosis rescue assays with wild-type vs. localization-defective mutants; endogenous PAK5 knockdown Molecular and cellular biology High 16581795
2006 PAK5 interacts with RhoD and RhoH in addition to Cdc42, and RhoD interaction targets PAK5 to subcellular locations distinct from those driven by Cdc42. The CRIB domain is critical for proper subcellular targeting. Kinase activity is required for PAK5 cycling on and off mitochondria; kinase-inactive PAK5 causes dramatic alterations in mitochondrial morphology. Deletion analysis; co-immunoprecipitation; subcellular localization by fluorescence microscopy; kinase-inactive mutant expression Biochemical and biophysical research communications Medium 17064668
2007 Crystal structures of all active, monophosphorylated group II PAK catalytic domains (PAK4, PAK5, PAK6) reveal catalytic domain plasticity including rearrangements of helix αC forming an additional helical turn and distortion of its C-terminus, interactions between conserved residues linking the glycine-rich loop, αC, and activation segment to anchor αC in an active conformation. A tri-substituted purine inhibitor was co-crystallized with PAK4 and PAK5. X-ray crystallography (multiple high-resolution structures); inhibitor screening and co-crystallization Structure High 17292838
2008 PAK5/PAK6 double-knockout mice are viable and fertile but exhibit locomotor deficits and learning/memory impairment, while PAK5 single-knockout mice show no gross abnormalities. PAK5 and PAK6 together are required for normal locomotion and cognitive function. Targeted gene disruption (double-knockout mice); behavioral testing (locomotion, learning/memory assays) Developmental biology High 18675265
2012 Using an analog-sensitive PAK5 mutant to selectively radiolabel substrates in murine brain extract, Pacsin1 and Synaptojanin1 were identified as novel PAK5 substrates. PAK5 (and other group II PAKs) phosphorylated Pacsin1 and Synaptojanin1 in vitro, and PAK5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo, implicating PAK5 in synaptic vesicle endocytosis and recycling. Analog-sensitive kinase substrate labeling in brain extract; in vitro kinase assay; co-immunoprecipitation (in vitro and in vivo) Proceedings of the National Academy of Sciences High 22371566
2013 PAK5 promotes breast cancer cell migration through a PAK5-Egr1-MMP2 signaling pathway; knockdown of PAK5 reduced Egr1 and MMP2 expression and inhibited migration and invasion. siRNA knockdown; western blot for pathway components; wound healing, migration and invasion assays Tumour biology Low 23696025
2013 PAK5 gain-of-function mutations in lung cancer activate the ERK pathway, and targeted depletion of mutated PAK5 inhibits proliferation and suppresses constitutive ERK pathway activation in lung cancer cells. Targeted genetic dependency screen; siRNA depletion; ERK pathway activation assays; proliferation assays Proceedings of the National Academy of Sciences Medium 23836671
2015 PAK5 phosphorylates GATA1 on Ser161 and Ser187; phosphorylated GATA1 recruits more HDAC3/4 to the E-cadherin promoter, leading to transcriptional repression of E-cadherin and promotion of EMT in breast cancer cells. GATA1 S161A/S187A mutant shows reduced HDAC3/4 recruitment. Co-immunoprecipitation; phosphorylation assay; HDAC recruitment assay; E-cadherin promoter reporter; site-directed mutagenesis; in vivo metastasis model Oncotarget Medium 25726523
2015 PAK5 interacts with and phosphorylates E47 transcription factor on Ser39 under HGF stimulation, promoting E47 nuclear accumulation via importin α, enhanced E47 binding to E-cadherin promoter, and EMT/metastasis in colon cancer. Co-immunoprecipitation; phosphorylation assay; importin α interaction assay; chromatin immunoprecipitation; xenograft metastasis model; site-directed mutagenesis Oncogene Medium 26212009
2016 PAK5 auto-activates through oligomerization mediated by a central domain (residues 109-420) that interferes with AID binding to the catalytic domain, maintaining high constitutive kinase activity. PAK4 is monomeric and inactive, while PAK5 is dimeric; removing oligomerization sequences suppresses PAK5 kinase activity. The PAK5 AID is functionally indistinguishable from PAK4 AID. Gel filtration (oligomerization); deletion analysis; in vitro kinase assay; cell imaging of puncta formation; AID domain swapping Biochemical journal Medium 27095851
2017 PAK5 phosphorylates SATB1 on Ser47, initiating EMT cascade and promoting migration and invasion of cervical cancer cells; PAK5 overexpression induces lung metastasis in xenograft models. Mn2+-Phos-tag SDS-PAGE; western blotting; immunofluorescence; dual luciferase reporter; xenograft metastasis; site-directed mutagenesis Cell death and differentiation Medium 30082769
2017 PAK5 promotes phosphorylation and nuclear translocation of NF-κB p65 subunit; nuclear p65 binds the Cyclin D1 promoter, increasing Cyclin D1 expression and promoting breast cancer cell cycle progression and proliferation. Co-IP confirmed PAK5-p65 interaction. Co-immunoprecipitation; phosphorylation assay; nuclear fractionation; Cyclin D1 promoter luciferase reporter; xenograft model; CCK-8 and flow cytometry Journal of experimental and clinical cancer research Medium 29041983
2018 PAK5 (PAK7) directly binds GSK3β and β-catenin, phosphorylates GSK3β to regulate β-catenin degradation, and activates the Wnt/β-catenin signaling pathway to promote breast cancer proliferation and migration. Co-immunoprecipitation; co-localization; TOP/FOP luciferase reporter; western blotting; functional proliferation and migration assays Journal of Cancer Medium 29805709
2018 PAK5 promotes EMT and cell migration/invasion in ovarian cancer by activating the PI3K/AKT pathway; PAK5 knockdown reduced phosphorylation of PI3K p85 at Tyr458 and AKT at Ser473. siRNA knockdown and overexpression; western blot for PI3K/AKT phosphorylation; wound healing and invasion assays Analytical cellular pathology Low 30245957
2018 PAK5 missense mutations in the serine-rich domain (S364L and D421N) drive aberrant melanocyte proliferation by activating ERK through kinase-independent mechanisms and activating PKA through kinase-dependent mechanisms, without affecting single-cell migration or temozolomide resistance. Stable expression of melanoma-associated PAK5 mutants in immortalized human melanocytes; proliferation assays; ERK and PKA activation assays; kinase-dead mutant analysis Oncotarget Medium 29875996
2019 PAK5 interacts with and phosphorylates DNPEP (aspartyl aminopeptidase) at Ser119, leading to downregulation of DNPEP and consequent upregulation of USP4; PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway, promoting breast cancer progression. Co-immunoprecipitation; phosphorylation assay; ubiquitin-proteasome pathway analysis; overexpression and knockdown; in vivo xenograft and metastasis models International journal of cancer Medium 31219614
2020 PAK5 interacts with Cdc42 and Integrin β1 and β3 in colorectal cancer cells, facilitating migration and invasion. Co-immunoprecipitation; knockdown; migration and invasion assays; in vitro and in vivo models Cancer medicine Low 32383357
2021 PAK5 is a brain mitochondrial kinase whose synthesis and signaling is spatiotemporally activated within axons in response to ischemic stress and axonal injury. PAK5 phosphorylates the mitochondrial anchor syntaphilin (SNPH), releasing the mitochondrial anchor and remobilizing damaged mitochondria to restore axonal energy supply. This axis is activated by upstream AKT signaling. In vitro neuronal injury and ischemia models; in vivo mouse brain injury models; PAK5 overexpression and knockdown; phosphorylation assay for SNPH; mitochondrial trafficking imaging; genetic rescue experiments Current biology High 34087103
2021 PAK5 phosphorylates DDX5 on Thr69; this phosphorylation promotes sumoylation of DDX5, stabilizing DDX5. Both phosphorylation and sumoylation of DDX5 enhance formation of a DDX5/Drosha/DGCR8 complex, promoting microRNA-10b processing and maturation, leading to breast cancer cell proliferation and metastasis. Co-immunoprecipitation; in vitro kinase assay; sumoylation assay; PAK5 knockout (MMTV-PyVT transgenic mice); miRNA processing assays; phospho-specific antibody validation Cell reports High 34936874
2021 PAK5 inhibits apoptosis by phosphorylating AIF at Thr281, inhibiting formation of the AIF/importin α3 complex and thereby preventing AIF nuclear translocation. PAK5 also decreases mitochondrial membrane permeability and maintains membrane potential to inhibit AIF release from mitochondria. Phosphorylation assay; co-immunoprecipitation (AIF/importin α3); mitochondrial membrane permeability and potential assays; nuclear fractionation; in vitro and in vivo breast cancer models International journal of biological sciences Medium 33867848
2022 14-3-3 interacts with PAK5 in response to phorbol ester-stimulated phosphorylation of Ser99 and EGF-stimulated phosphorylation of Ser288; these phosphorylations regulate PAK5 localization and signaling in melanoma cells. 14-3-3 binding assay; phosphosite mapping; phorbol ester and EGF stimulation; co-immunoprecipitation; cell localization studies Biochemical journal Medium 35969127
2023 PAK5 binds to and phosphorylates Slug (SNAI2) at Ser87; phosphorylated Slug transactivates N-cadherin expression, promoting EMT and metastasis in renal cell carcinoma. Co-immunoprecipitation; phosphorylation assay; western blot; xenograft metastasis model; site-directed mutagenesis Cellular signalling Medium 37437827
2022 PAK5 interacts with transcription factors LMO2 and GATA1 in the nucleus after mitochondria-to-nucleus translocation; without LMO2, PAK5 fails to bind GATA1 and phosphorylate it at Ser161, indicating LMO2 is required as a co-factor for PAK5-mediated GATA1 phosphorylation in hematopoietic cells. Co-immunoprecipitation; nuclear fractionation; phosphorylation assay; serum-stimulated nuclear translocation assay Cellular and molecular biology Low 36905268
2024 PAK5 phosphorylates PKM2 at Ser519, enhancing PKM2 protein stability and promoting anaerobic glycolysis in endometriosis. PAK5 inhibition or knockout blocks endometriosis development. In vitro kinase assay; site-directed mutagenesis; PAK5 knockout mice; pharmacological inhibition (GNE-2861); glycolysis assays; cell proliferation and metastasis assays Frontiers of medicine Medium 39331255
2025 PAK5 phosphorylates METTL14 on Ser399 to enhance m6A modification of lncRNA MALAT1, increasing MALAT1 stability; stabilized MALAT1 inhibits USP8-mediated deubiquitination of nuclear HER2, promoting N-HER2 accumulation and trastuzumab resistance in HER2-positive breast cancer. Co-immunoprecipitation; m6A modification assay; phosphorylation assay; MALAT1 stability assay; USP8-N-HER2 interaction assay; in vitro and in vivo models Cell death and disease Medium 40258843
2026 PAK5 interacts with and phosphorylates HMGCS2 at Ser138 and Ser311, suppressing intracellular β-hydroxybutyrate synthesis. Ser138 phosphorylation recruits E3 ubiquitin ligase BMI1 to facilitate HMGCS2 degradation; Ser311 phosphorylation reduces HMGCS2 enzymatic activity by inhibiting SIRT3-dependent deacetylation. This PAK5-HMGCS2 pathway promotes breast cancer metastasis. Co-immunoprecipitation; in vitro kinase assay; site-directed mutagenesis; ubiquitination assay; SIRT3 deacetylation assay; β-HB metabolite measurement; in vitro and in vivo breast cancer models; ketogenic diet rescue Cancer research High 41834498
2026 PAK5 promotes dynamin-related protein 1 (Drp1) activation, leading to mitochondrial midzone division, reduced Mfn1 expression, and enhanced expression of proliferative proteins (PCNA, Cyclin A, Cyclin D) in pulmonary artery smooth muscle cells, driving vascular remodeling in hypoxic pulmonary hypertension. In vivo PAK5-silencing mouse model; in vitro hypoxia model; western blot for Drp1, Mfn1, and cell cycle proteins; mitochondrial morphology analysis; hemodynamic measurements Scientific reports Medium 41927885
2021 PAK5 promotes SOX2 phosphorylation in lung squamous cell carcinoma cells, maintaining cancer stem cell-like self-renewal ability; PAK5 absence abolishes SOX2 expression and phosphorylation, reducing oncosphere formation in vitro and tumor growth in vivo. Co-immunoprecipitation; western blotting; oncosphere-forming assay; xenograft model; PAK5 knockdown and overexpression Experimental cell research Low 32721391

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells. Molecular and cellular biology 141 11756552
2003 p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD. Molecular and cellular biology 140 12897128
2002 Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain. Oncogene 107 12032833
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
2017 MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5. Cell death & disease 76 29072688
2008 Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion. Developmental biology 72 18675265
2021 Reprogramming an energetic AKT-PAK5 axis boosts axon energy supply and facilitates neuron survival and regeneration after injury and ischemia. Current biology : CB 70 34087103
2005 PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable microtubules and dynamic actin. Molecular biology of the cell 67 16014608
2006 Nucleocytoplasmic shuttling of Pak5 regulates its antiapoptotic properties. Molecular and cellular biology 57 16581795
2003 Targeted disruption of the gene for the PAK5 kinase in mice. Molecular and cellular biology 55 14517284
2013 Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer. Proceedings of the National Academy of Sciences of the United States of America 51 23836671
2015 GATA1 induces epithelial-mesenchymal transition in breast cancer cells through PAK5 oncogenic signaling. Oncotarget 50 25726523
2013 PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 47 23696025
2017 PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo. Journal of experimental & clinical cancer research : CR 43 29041983
2015 miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma. Biochemical and biophysical research communications 41 26116538
2013 Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway. Brain tumor pathology 40 24062079
2018 PAK5 promotes the migration and invasion of cervical cancer cells by phosphorylating SATB1. Cell death and differentiation 36 30082769
2006 Multiple Rho proteins regulate the subcellular targeting of PAK5. Biochemical and biophysical research communications 36 17064668
2015 PAK5-mediated E47 phosphorylation promotes epithelial-mesenchymal transition and metastasis of colon cancer. Oncogene 35 26212009
2014 An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis. Human molecular genetics 30 24474471
2019 A PAK5-DNPEP-USP4 axis dictates breast cancer growth and metastasis. International journal of cancer 28 31219614
2023 HPV E7-drived ALKBH5 promotes cervical cancer progression by modulating m6A modification of PAK5. Pharmacological research 27 37480971
2021 PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer. Cell reports 25 34936874
2018 P21-activated kinase 7 (PAK7) interacts with and activates Wnt/β-catenin signaling pathway in breast cancer. Journal of Cancer 25 29805709
2013 The overexpression of P21-activated kinase 5 (PAK5) promotes paclitaxel-chemoresistance of epithelial ovarian cancer. Molecular and cellular biochemistry 25 23877225
2012 Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking. Proceedings of the National Academy of Sciences of the United States of America 25 22371566
2009 Combined inhibition of PAK7, MAP3K7 and CK2alpha kinases inhibits the growth of MiaPaCa2 pancreatic cancer cell xenografts. Cancer gene therapy 24 19363471
2021 MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated β-catenin/ABCB1 signaling pathway. Journal of biomedical science 23 34340705
2013 Functional deficits in PAK5, PAK6 and PAK5/PAK6 knockout mice. PloS one 23 23593460
2004 RSK4 and PAK5 are novel candidate genes in diabetic rat kidney and brain. Molecular pharmacology 21 15615695
2015 Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5. International journal of biological sciences 20 25632266
2017 PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells. The Biochemical journal 19 28232500
2022 Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition. Biomedicines 18 36672609
2021 PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis. International journal of biological sciences 18 33867848
2020 Long non-coding RNA SOX21-AS1 promotes cell proliferation and invasion through upregulating PAK7 expression by sponging miR-144-3p in glioma cells. Neoplasma 17 31973536
2014 An oncogenic kinase: putting PAK5 forward. Expert opinion on therapeutic targets 17 24869804
2019 Human p21-activated kinase 5 (PAK5) expression and potential mechanisms in relevant cancers: Basic and clinical perspectives for molecular cancer therapeutics. Life sciences 16 31805288
2018 PAK5 Induces EMT and Promotes Cell Migration and Invasion by Activating the PI3K/AKT Pathway in Ovarian Cancer. Analytical cellular pathology (Amsterdam) 15 30245957
2021 MiR-145-5p modulates lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia. Canadian journal of physiology and pharmacology 13 34143694
2020 PAK5 facilitates the proliferation, invasion and migration in colorectal cancer cells. Cancer medicine 13 32383357
2017 MicroRNA-492 overexpression exerts suppressive effects on the progression of osteosarcoma by targeting PAK7. International journal of molecular medicine 13 28677719
2020 PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas. Experimental cell research 11 32721391
2017 PAK5 overexpression is associated with lung metastasis in osteosarcoma. Oncology letters 10 29434926
2016 PAK5 is auto-activated by a central domain that promotes kinase oligomerization. The Biochemical journal 10 27095851
2022 The Predictive Value of PAK7 Mutation for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Cancer. Frontiers in immunology 8 35242138
2021 Inhibiting p21-activated kinase (PAK7) enhances radiosensitivity in hepatocellular carcinoma. Human & experimental toxicology 7 34165002
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
2024 PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis. Frontiers of medicine 5 39331255
2025 PAK5 promotes the trastuzumab resistance by increasing HER2 nuclear accumulation in HER2-positive breast cancer. Cell death & disease 4 40258843
2022 Differential roles and regulation of the protein kinases PAK4, PAK5 and PAK6 in melanoma cells. The Biochemical journal 4 35969127
2019 miR‑489 promotes apoptosis and inhibits invasiveness of glioma cells by targeting PAK5/RAF1 signaling pathways. Oncology reports 4 31638257
2023 PAK5 potentiates slug transactivation of N-cadherin to facilitate metastasis of renal cell carcinoma. Cellular signalling 3 37437827
2018 Melanoma-associated mutants within the serine-rich domain of PAK5 direct kinase activity to mitogenic pathways. Oncotarget 3 29875996
2023 [Retracted] miR‑489 promotes apoptosis and inhibits invasiveness of glioma cells by targeting PAK5/RAF1 signaling pathways. Oncology reports 2 37165914
2026 PAK5-Mediated Suppression of β-Hydroxybutyrate Production Promotes Breast Cancer Metastasis and Can Be Overcome with Ketogenic Diet. Cancer research 0 41834498
2026 PAK5 drives vascular remodeling in hypoxic pulmonary hypertension via Drp1-dependent mitochondrial midzone division. Scientific reports 0 41927885
2026 Buyang Huanwu decoction promotes neurological recovery after ischemic stroke by activating the Akt/PAK5/SNPH axis to enhance mitochondrial recruitment and axonal remodeling. Journal of ethnopharmacology 0 42134501
2025 The role and mechanism of PAK5 in the development and immunotherapy of oral squamous cell carcinoma. International immunopharmacology 0 40876424
2025 PAK5 Promotes Esophageal Squamous Cell Carcinoma Progression Revealed by Transcriptomic Profiling. Journal of visualized experiments : JoVE 0 41490050
2024 MiR-302 targets PAK5 and prevents the transition from chronic hepatitis B to liver cirrhosis. JPMA. The Journal of the Pakistan Medical Association 0 39658980
2022 PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1. Cellular and molecular biology (Noisy-le-Grand, France) 0 36905268

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