Property Summary

NCBI Gene PubMed Count 89
PubMed Score 170.94
PubTator Score 89.43

Knowledge Summary

Patent (17,386)

TINX Plot

  Disease (2)

Expression

  Differential Expression (5)

Disease log2 FC p
malignant mesothelioma 1.900 1.7e-07
osteosarcoma 1.224 2.8e-03
atypical teratoid / rhabdoid tumor 1.300 3.2e-09
glioblastoma 1.200 2.7e-07
medulloblastoma, large-cell 1.100 1.3e-05

Protein-protein Interaction (6)

Gene RIF (64)

PMID Text
26841865 PAK4 methylation by SETD6 promotes the activation of the Wnt/beta-catenin pathway.
26607847 PAK4 catalytic domain binds cellular ATP and the Inka1 inhibitor. The crystal lattice consists only of PAK4-PAK4 contacts, which form a hexagonal array with channels of 80 A in diameter that run the length of the crystal.
26598620 PAK4 and RhoU cooperate to drive adhesion turnover and promote cell migration.
26546043 data show decreased nuclear accumulation and transcriptional activity of STAT3 in PAK4-silenced pancreatic cancer cells
26411419 Study has confirms prognostic role of PAK4 level in cervical cancer patients and recognizes the regulatory role in cervical cancer progression. PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way.
26218748 Nuclear Pak4 is involved in the pathogenesis of endometrial cancer especially in postmenopausal women.
26124003 this report reveals that high level of p-Pak4 correlates with poor prognosis in gastric cancer (GC), thereby suggesting that p-Pak4 might be a potential prognostic marker for GC.
26068882 PAK4 localizes to cell-cell junctions and contributes to estblishing cell polarity.PAK4 phosphorylate beta-catenin Serine-675.PAK4 binding to cell-cell junctions is dependent on Cdc42.
25975262 PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC.
25791829 PAK1 and PAK4 expression were associated with colorectal cancer metastasis and infiltration
25662318 PAK4 phosphorylates Par6B at Ser143 blocking its interaction with Cdc42.
25637478 Increased Pak4 expression can lead to development of adenomyosis by enhancing the invasiveness of endometrial cells through regulation of MMP-2 and -9 activities.
25560280 PAK4 promotes alpha-MSH/UVB-induced melanogenesis via the CREB and Wnt/beta-catenin signaling pathways and suggest that PAK4 may be a potential therapeutic target in pigmentation disorders.
25410752 microRNA-433 (miRNA-433 directly targets PAK4 through the miRNA-433 binding sequence at the 3'-UTR of PAK4 mRNA.
25359780 CXCL12/CXCR4 signaling has a role in docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIMK1
25238288 Suggest that PAK4 is a regulator of NF-kappaB pathway in pancreatic cancer cells, controlling cell proliferation and survival.
24829151 PAK4 is known to act as a transporter for beta-catenin nuclear translocation.
24704155 Both indole and indazole of KY-04031 are responsible for PAK4 hinge interaction.
24374310 Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4.
24366569 p21-activated kinase 4 inhibitor PF-3758309 shows anti-metastatic effect.
23934187 The results document an oncogenic role of PAK4 in repression of Smad2/3 transactivation that involved in tumorigenesis, and suggest PAK4 as a potential therapeutic target for gastric cancer.
23893240 PAK4-SCG10 signaling occurs in gastric cancer cell invasion.
23841590 PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1).
23790167 Pak4 is an important regulator of Endometrial cancer cell migration and invasion
23652058 Genotype TT for rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success.
23642861 PAK4 should be considered a signalling integrator regulating numerous fundamental cellular processes. [Review]
23293332 increased expression of Pak4 might lead to the establishment and progression of endometriosis by enhanced cellular viability and invasiveness in endometrial cells.
23254288 Interaction between PAK4 and MMP-2 regulated anoikis, cell migration and invasion in glioma.
23233484 Results support a role for the PAK4 and PAK1 in the proliferation of mutant KRAS-driven colorectal carcinoma cells via pathways not involving RAF/MEK/ERK and PI3K/AKT signaling.
23229348 we confirmed that the mechanisms of the Pak4-induced cell cycle arrest invovlve the activation of the ATM/Chk1/2/p53 pathway.
22988085 Full-length PAK4 is constitutively autoinibited, but mutation of the pseudosubstrate releases this inhibition.
22766504 these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.
22710715 PAK4 regulated cAMP-induced neuroendocrine differentiation, which is known to promote tumor progression.in prostate neoplasms
22689056 Overexpression of PAK4 harbouring a somatic mutation, E329K, increased the HGF-driven motility of metastatic prostate carcinoma cells.
22653441 PAK4 is strongly inhibited by an auto-inhibitory domain formed by amino acids 20 to 68.
22450748 PAK4 is required for metaphase spindle positioning and anchoring.
22085492 Small-molecule PAK4 kinase inhibitor LCH- 7749944 was identified to be capable of inhibiting PAK4 signaling pathways and suppressing PAK4-mediated gastric cancer cell behaviors including proliferation, migration and invasion.
21832093 PKD can also regulate LIMK through direct phosphorylation and activation of its upstream kinase p21-activated kinase 4 (PAK4).
21385901 Findings reveal that CDK5RAP3 is widely overexpressed in hepatocellular carcinoma and that overexpression of CDK5RAP3 promotes HCC metastasis through PAK4 activation
21325635 Overexpression of PAK4 is associated with gestational trophoblastic disease.
20926745 Pak4 overexpression promoted ovarian cancer cell migration and invasion in a c-Src, MEK-1, MMP2, and kinase-dependent manner, and induced cell proliferation through the Pak4/c-Src/EGFR pathway that controls cyclin D1 and CDC25A expression.
20719960 PAK4 is activated by cell attachment to vitronectin as mediated by PAK4 binding partner integrin alphavbeta5.
20631255 This study demonstrates that controlled regulation of PAK4 is required for apical junction formation in lung epithelial cells and highlights potential cross-talk between two Cdc42 targets, PAK4 and Par6B.
20578242 Data show that active PAK4 can affect (cap-independent) translation from specific IRES sequences in vivo, and that the N-terminal domain is critical for this regulation.
20564219 Data show that both Pak5 and constitutively active Pak4, the founding member of the Group B Paks, directly phosphorylate p120 in vitro.
20507994 p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-762 regulates cell migration
20501374 PAK4 is closely correlated to the progression and metastasis of breast cancer.
20406887 regulates prostate cancer cell adhesion
19778628 DGCR6L, a novel PAK4 interacting protein, regulated PAK4-mediated migration of human gastric cancer cells via LIMK1.
19594544 PAK4 overexpression through amplification or other mechanisms promotes the proliferation and/or survival of oral squamous-cell carcinoma cells
19460752 Knockdown of p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells
19050074 Like RIOK3, PAK4 promotes pancreas ductal cell motility and invasion in pancreatic cancer
18836286 although the PAK4 gene is not activated by mutation in cell lines with gene amplification, an oncogenic form of the KRAS2 gene is present in these cells and oncogenic KRAS2 can activate PAK4
18782768 pneumolysin selectively induced expression of MKP1 via a TLR4-dependent MyD88-TRAF6-ERK pathway, which inhibited the PAK4-JNK signaling pathway,leading to up-regulation of MUC5AC mucin production
18636970 human Mbt homologue PAK4 leads to anchorage-independent growth and provide a functional link between a PAK protein and the cadherin-catenin complex.
18628988 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
18424072 These results support a model whereby hepatocyte growth factor-stimulated cell migration also requires a cofilin phosphorylation step that is mediated by PAK4.
18319301 RNAi-mediated or dominant-negative suppression of Pak4, major regulators of cytoskeletal signaling downstream of Cdc42 or Rac1, markedly inhibits EC lumen and tube formation.
17555715 bring novel insights into our understanding of synergistic regulation of MUC5AC mucin by both pathological and physiological inducers
16897755 PAK4 and alphaPIX can induce highly localized changes in actin dynamics and thereby regulate size and number of podosomes in primary human macrophages.
16227624 PAK4 has a role in TNF-alpha induced cell survival pathyways by facilitating TRADD binding to the TNF Receptor
15827085 PAK4 mediates morphological changes through regulation of GEF-H1
14625312 PAK4 can negatively regulate the activation of Rho through a direct protein-protein interaction with G protein-linked Rho GEFs
12529371 PAK4 interacts with KGF receptor and mediate anti-apoptosis effects of KGF on epithelial cells.

AA Sequence

MFGKRKKRVEISAPSNFEHRVHTGFDQHEQKFTGLPRQWQSLIEESARRPKPLVDPACITSIQPGAPKTI      1 - 70
VRGSKGAKDGALTLLLDEFENMSVTRSNSLRRDSPPPPARARQENGMPEEPATTARGGPGKAGSRGRFAG     71 - 140
HSEAGGGSGDRRRAGPEKRPKSSREGSGGPQESSRDKRPLSGPDVGTPQPAGLASGAKLAAGRPFNTYPR    141 - 210
ADTDHPSRGAQGEPHDVAPNGPSAGGLAIPQSSSSSSRPPTRARGAPSPGVLGPHASEPQLAPPACTPAA    211 - 280
PAVPGPPGPRSPQREPQRVSHEQFRAALQLVVDPGDPRSYLDNFIKIGEGSTGIVCIATVRSSGKLVAVK    281 - 350
KMDLRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIAAV    351 - 420
CLAVLQALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSLVGTPYWMAPELISRL    421 - 490
PYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPRLKNLHKVSPSLKGFLDRLLVRDPAQR    491 - 560
ATAAELLKHPFLAKAGPPASIVPLMRQNRTR                                           561 - 591
//

Text Mined References (106)

PMID Year Title
26841865 2016 PAK4 Methylation by SETD6 Promotes the Activation of the Wnt/?-Catenin Pathway.
26607847 2015 An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1.
26598620 2015 PAK4 promotes kinase-independent stabilization of RhoU to modulate cell adhesion.
26546043 2016 p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling.
26411419 2015 PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.
26218748 2015 p21-Activated Kinases 1, 2 and 4 in Endometrial Cancers: Effects on Clinical Outcomes and Cell Proliferation.
26124003 2015 Activated Pak4 expression correlates with poor prognosis in human gastric cancer patients.
26068882 2015 The Cdc42 Effector Kinase PAK4 Localizes to Cell-Cell Junctions and Contributes to Establishing Cell Polarity.
25975262 2015 Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion.
25791829 2015 P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration.
25662318 2015 Functional cross-talk between Cdc42 and two downstream targets, Par6B and PAK4.
25637478 2015 Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells.
25560280 2015 p21-activated kinase 4 critically regulates melanogenesis via activation of the CREB/MITF and ?-catenin/MITF pathways.
25468996 2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
25410752 2015 MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4).
25359780 2014 CXCL12/CXCR4 signaling counteracts docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIM domain kinase 1.
25238288 2014 p-21 activated kinase 4 promotes proliferation and survival of pancreatic cancer cells through AKT- and ERK-dependent activation of NF-?B pathway.
25074804 2014 Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure.
24829151 2014 The metastasis suppressor NDRG1 modulates the phosphorylation and nuclear translocation of ?-catenin through mechanisms involving FRAT1 and PAK4.
24704155 2014 Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor.
24374310 2014 Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.
24366569 2014 PF-3758309, p21-activated kinase 4 inhibitor, suppresses migration and invasion of A549 human lung cancer cells via regulation of CREB, NF-?B, and ?-catenin signalings.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24255178 2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions.
24129315 2014 Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.
23934187 2014 Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis.
23893240 2014 PAK4 kinase-mediated SCG10 phosphorylation involved in gastric cancer metastasis.
23841590 2013 Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4.
23790167 2013 p21-activated kinase 4 regulation of endometrial cancer cell migration and invasion involves the ERK1/2 pathway mediated MMP-2 secretion.
23652058 2013 Gene polymorphisms of interleukin-28, p21-activated protein kinases 4, and response to interferon-? based therapy in Chinese patients with chronic hepatitis B.
23642861 P21-activated kinase 4--not just one of the PAK.
23293332 2013 Regulation of P21-activated kinase-4 by progesterone and tumor necrosis factor-? in human endometrium and its increased expression in advanced-stage endometriosis.
23254288 2012 Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma.
23233484 2013 Knockdown of PAK4 or PAK1 inhibits the proliferation of mutant KRAS colon cancer cells independently of RAF/MEK/ERK and PI3K/AKT signaling.
23229348 2013 Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22988085 2012 Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate.
22766504 2012 MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells.
22710715 2013 p21-Activated kinase 4 promotes prostate cancer progression through CREB.
22689056 2013 PAK4 kinase activity and somatic mutation promote carcinoma cell motility and influence inhibitor sensitivity.
22653441 2012 Group I and II mammalian PAKs have different modes of activation by Cdc42.
22450748 2013 P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.
22085492 2012 LCH-7749944, a novel and potent p21-activated kinase 4 inhibitor, suppresses proliferation and invasion in human gastric cancer cells.
21832093 2011 Protein kinase D regulates cofilin activity through p21-activated kinase 4.
21423176 2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for ?-Pix in negative regulation of focal adhesion maturation.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21385901 2011 Overexpression of a novel activator of PAK4, the CDK5 kinase-associated protein CDK5RAP3, promotes hepatocellular carcinoma metastasis.
21325635 2011 Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma.
21269460 2011 Initial characterization of the human central proteome.
21044950 2011 Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
20936779 2010 A human MAP kinase interactome.
20926745 2010 p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients.
20805321 2010 Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis.
20719960 2010 Integrin-mediated cell attachment induces a PAK4-dependent feedback loop regulating cell adhesion through modified integrin alpha v beta 5 clustering and turnover.
20631255 2010 Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B.
20578242 2010 N-terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals.
20564219 2010 p120-catenin is a binding partner and substrate for Group B Pak kinases.
20507994 2010 p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-762 regulates cell migration.
20501374 2010 [Expression of PAK4 in breast cancer and benign breast pathological changes].
20406887 2010 PAK4: a pluripotent kinase that regulates prostate cancer cell adhesion.
20070256 2010 The emerging importance of group II PAKs.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19778628 2010 DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19594544 2009 Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19050074 2008 Genomic alterations link Rho family of GTPases to the highly invasive phenotype of pancreas cancer.
18836286 2008 Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification.
18782768 2008 MKP1 regulates the induction of MUC5AC mucin by Streptococcus pneumoniae pneumolysin by inhibiting the PAK4-JNK signaling pathway.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18636970 2008 The Drosophila p21-activated kinase Mbt modulates DE-cadherin-mediated cell adhesion by phosphorylation of Armadillo.
18628988 2008 Neither replication nor simulation supports a role for the axon guidance pathway in the genetics of Parkinson's disease.
18424072 2008 A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF.
18319301 2008 Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17555715 2007 Opposing roles of PAK2 and PAK4 in synergistic induction of MUC5AC mucin by bacterium NTHi and EGF.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
17192257 2007 Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16897755 2006 PAK4 and alphaPIX determine podosome size and number in macrophages through localized actin regulation.
16381901 2006 The LIFEdb database in 2006.
16227624 2005 PAK4 functions in tumor necrosis factor (TNF) alpha-induced survival pathways by facilitating TRADD binding to the TNF receptor.
16169070 2005 A human protein-protein interaction network: a resource for annotating the proteome.
15827085 2005 PAK4 mediates morphological changes through the regulation of GEF-H1.
15660133 2005 Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15345747 2004 Phosphoproteomic analysis of the developing mouse brain.
15324660 2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization.
15161933 2004 Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14625312 2004 Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor.
14560027 2003 Death receptor-induced activation of initiator caspase 8 is antagonized by serine/threonine kinase PAK4.
12529371 2003 p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte growth factor receptor and participates in keratinocyte growth factor-mediated inhibition of oxidant-induced cell death.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12356872 2002 P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration.
11950587 2002 p21-activated kinases: three more join the Pak.
11413130 2001 Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin.
11313478 2001 Activated PAK4 regulates cell adhesion and anchorage-independent growth.
11278822 2001 The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10574461 1999 Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.
10461188 1999 Pak to the future.
9822598 1998 PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia.