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| PAK4SummaryGene Symbol: PAK4 Description: p21 (RAC1) activated kinase 4 Alias: serine/threonine-protein kinase PAK 4, p21 protein (Cdc42/Rac)-activated kinase 4, p21(CDKN1A)-activated kinase 4, protein kinase related to S. cerevisiae STE20, effector for Cdc42Hs Species: human Products: PAK4 Top Publications
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- Lu Y, Pan Z, Devaux Y, Ray P. 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. J Biol Chem. 2003;278:10374-80 pubmed..The PAKs are regulated by the Rho-family GTPases Rac and Cdc42. PAK4 is the most divergent member of the PAK family of proteins and may have distinct functions...
- Menzel N, Melzer J, Waschke J, Lenz C, Wecklein H, Lochnit G, et al. The Drosophila p21-activated kinase Mbt modulates DE-cadherin-mediated cell adhesion by phosphorylation of Armadillo. Biochem J. 2008;416:231-41 pubmed publisher..present study, we address this question using the Drosophila PAK protein Mbt, which is most similar to vertebrate PAK4. Previous phenotypic analysis showed that Mbt has a function to maintain adherens junctions during eye development ..
- Wells C, Whale A, Parsons M, Masters J, Jones G. PAK4: a pluripotent kinase that regulates prostate cancer cell adhesion. J Cell Sci. 2010;123:1663-73 pubmed publisher..Rho-family GTPases orchestrate both of these cellular processes. p21-activated kinase 4 (PAK4), a specific effector of the Rho GTPase Cdc42, is activated by HGF, and we have previously shown that activated ..
- Baldassa S, Calogero A, Colombo G, Zippel R, Gnesutta N. N-terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals. J Cell Physiol. 2010;224:722-33 pubmed publisherThe serine/threonine kinase PAK4 is a Rho GTPases effector protein implicated in many critical biological processes, including regulation of cell morphology and motility, embryonic development, cell survival, response to infection, and ..
- Li Z, Lock J, Olofsson H, Kowalewski J, Teller S, Liu Y, et al. Integrin-mediated cell attachment induces a PAK4-dependent feedback loop regulating cell adhesion through modified integrin alpha v beta 5 clustering and turnover. Mol Biol Cell. 2010;21:3317-29 pubmed publisher..This autoinhibitory negative feedback loop is initiated by cell adhesion to vitronectin, leading to PAK4 activation, which in turn limits total cell-vitronectin adhesion strength...
- Callow M, Zozulya S, Gishizky M, Jallal B, Smeal T. PAK4 mediates morphological changes through the regulation of GEF-H1. J Cell Sci. 2005;118:1861-72 pubmed..Here we show that p21-activated-kinase 4 (PAK4) mediates morphological changes through its association with the Rho-family guanine nucleotide exchange factor (GEF)..
- Li Z, Zhang H, Lundin L, Thullberg M, Liu Y, Wang Y, et al. p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-762 regulates cell migration. J Biol Chem. 2010;285:23699-710 pubmed publisher..In addition, we previously found a role for p21-activated kinase 4 (PAK4) in selective regulation of integrin alphavbeta5-mediated cell motility (Zhang, H., Li, Z., Viklund, E. K...
- Chen S, Auletta T, Dovirak O, Hutter C, Kuntz K, El ftesi S, et al. Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification. Cancer Biol Ther. 2008;7:1793-802 pubmed..cancer and demonstrate how boundaries of common regions of mutation can be mapped and how a gene, in this case PAK4 amplified on chromosome19q13, can be functionally validated...
- Li X, Ke Q, Li Y, Liu F, Zhu G, Li F. DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1. Int J Biochem Cell Biol. 2010;42:70-9 pubmed publisherOverexpression, genetic amplification and mutations of p21-activated kinase 4 (PAK4) were found in a variety of human cancers. PAK4 regulated actin cytoskeleton reorganization by phosphorylating LIMK1 and promoted cancer cells migration...
- Bompard G, Rabeharivelo G, Frank M, Cau J, Delsert C, Morin N. Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis. J Cell Biol. 2010;190:807-22 pubmed publisher..Here, we identify a novel level of Ran regulation. We show that Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation on serine-135 increases during mitosis...
- Siu M, Chan H, Kong D, Wong E, Wong O, Ngan H, et al. p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients. Proc Natl Acad Sci U S A. 2010;107:18622-7 pubmed publisher..In this study, we present a role for p21-activated kinase 4 (Pak4) in ovarian cancer progression...
- Kesanakurti D, Chetty C, Rajasekhar Maddirela D, Gujrati M, Rao J. Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma. Cell Death Dis. 2012;3:e445 pubmed publisher..4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 (PAK4) inhibition, prompting us to further investigate the role of PAK4 in glioma...
- Dan C, Kelly A, Bernard O, Minden A. Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. J Biol Chem. 2001;276:32115-21 pubmedb>PAK4 is the most recently identified member of the PAK family of serine/threonine kinases. PAK4 differs from other members of the PAK family in sequence and in many of its functions...
- Ahmed T, Shea K, Masters J, Jones G, Wells C. A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF. Cell Signal. 2008;20:1320-8 pubmed publisher..p21 activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is activated downstream of HGF...
- Park M, Lee H, Lee C, You S, Kim D, Park B, et al. p21-Activated kinase 4 promotes prostate cancer progression through CREB. Oncogene. 2013;32:2475-82 pubmed publisher..The present study investigated a role for p21-activated kinase 4 (PAK4) in prostate cancer progression...
- Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, et al. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005;24:473-86 pubmed..consisting of SSH-1L, LIMK1, actin, and the scaffolding protein, 14-3-3zeta, is involved, along with the kinase, PAK4, in the regulation of ADF/cofilin activity...
- Li X, Minden A. PAK4 functions in tumor necrosis factor (TNF) alpha-induced survival pathways by facilitating TRADD binding to the TNF receptor. J Biol Chem. 2005;280:41192-200 pubmedb>PAK4 is a member of the group B family of p21-activated kinases. Its expression is elevated in many cancer cell lines, and activated PAK4 is highly transforming, suggesting that it plays an important role in tumorigenesis...
- Zhong N, Shi S, Wang H, Wu G, Wang Y, Ma Q, et al. Silencing Aurora-A with siRNA inhibits cell proliferation in human lung adenocarcinoma cells. Int J Oncol. 2016;49:1028-38 pubmed publisher..inhibition induced cell cycle arrest and apoptosis are associated with downregulated RAF-1, CCND2, CCND3, CDK4, PAK4, EGFR and upregulated WEE1 expression...
- Kumar R, Sanawar R, Li X, Li F. Structure, biochemistry, and biology of PAK kinases. Gene. 2017;605:20-31 pubmed publisher..We give special emphasis to PAK1 and PAK4, the prototypes of groups I and II, for their profound roles in cancer, the nervous system, and the heart...
- Azmi A, Li Y, Muqbil I, Aboukameel A, Senapedis W, Baloglu E, et al. Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration. Oncotarget. 2017;8:82144-82155 pubmed publisher..compound treatment mediated the down-regulation of known miR-145 targets genes including EGFR, MMP1, MT-MMP, c-Myc, Pak4 and Sox-2...
- Li W, Hu N, Wang Z, Yu K, Su H, Wang L, et al. Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population. PLoS ONE. 2013;8:e68999 pubmed publisher..72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05)...
- Morse E, Sun X, Olberding J, Ha B, Boggon T, Calderwood D. PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape. J Cell Sci. 2016;129:380-93 pubmed publisher..Finally, we demonstrate that all type II PAKs (PAK4, PAK5 and PAK6) target to cell-cell adhesions, albeit to differing extents, but PAK1 (a type I PAK) does not...
- Hodge R, Ridley A. Regulation and functions of RhoU and RhoV. Small Gtpases. 2017;:1-8 pubmed publisher..Similar to Rac and Cdc42, they interact with PAK serine/threonine kinases, and in the case of PAK4, this interaction leads to RhoU protein stabilization...
- Cosset E, Ilmjärv S, Dutoit V, Elliott K, von Schalscha T, Camargo M, et al. Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma. Cancer Cell. 2017;32:856-868.e5 pubmed publisher..and "classical" subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression...
- Lee S, Cieply B, Yang Y, Peart N, Glaser C, Chan P, et al. Esrp1-Regulated Splicing of Arhgef11 Isoforms Is Required for Epithelial Tight Junction Integrity. Cell Rep. 2018;25:2417-2430.e5 pubmed publisher..Mesenchymal Arhgef11 transcripts contain a C-terminal exon that binds to PAK4 and inhibits RhoA activation byArhgef11...
- Fiedler J, Jazbutyte V, Kirchmaier B, Gupta S, Lorenzen J, Hartmann D, et al. MicroRNA-24 regulates vascularity after myocardial infarction. Circulation. 2011;124:720-30 pubmed publisher..are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays...
- Walther R, Burki M, Pinal N, Rogerson C, Pichaud F. Rap1, Canoe and Mbt cooperate with Bazooka to promote zonula adherens assembly in the fly photoreceptor. J Cell Sci. 2018;131: pubmed publisher..Altogether, we propose the Dizzy, Rap1 and Cno pathway and Mbt converge in regulating the interface between Bazooka and AJ material to promote ZA morphogenesis. ..
- Whale A, Dart A, Holt M, Jones G, Wells C. PAK4 kinase activity and somatic mutation promote carcinoma cell motility and influence inhibitor sensitivity. Oncogene. 2013;32:2114-20 pubmed publisher..p21-activated kinase 4 (PAK4), a potential therapeutic target, is recruited to and activated by c-Met...
- Vargas B, Giacobbi N, Sanyal A, Venkatachari N, Han F, Gupta P, et al. Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency. Antimicrob Agents Chemother. 2019;63: pubmed publisher..Of these, danusertib, an Aurora kinase inhibitor, and PF-3758309, a PAK4 inhibitor, were the most potent...
- Law S, Sargent T. Maternal pak4 expression is required for primitive myelopoiesis in zebrafish. Mech Dev. 2013;130:181-94 pubmed publisherTranscripts of pak4, the zebrafish ortholog of p21-activated kinase 4 (PAK4), are most abundant in the egg and fall to low levels by the end of gastrulation, after which expression is essentially ubiquitous...
- Franovic A, Elliott K, Seguin L, Camargo M, Weis S, Cheresh D. Glioblastomas require integrin αvβ3/PAK4 signaling to escape senescence. Cancer Res. 2015;75:4466-73 pubmed publisher..novel tissue-specific effector mechanism involving recruitment and activation of the cytoskeletal regulatory kinase PAK4. Mechanistically, targeting either αvβ3 or PAK4 led to emergence of a p21-dependent, p53-independent cell ..
- Yang Y, Zhou Q, Chen X, Yan B, Guo X, Zhang H, et al. Profiling of differentially expressed genes in sheep T lymphocytes response to an artificial primary Haemonchus contortus infection. Parasit Vectors. 2015;8:235 pubmed publisher..analysis of significant differentially expressed genes, such as SLC9A3R2, ABCB9, COMMD4, SUGT1, FCER1G, GSK3A, PAK4 and FCER2, revealed a crucial association with cellular homeostasis maintenance and immune response...
- Spratley S, Bastea L, Döppler H, Mizuno K, Storz P. Protein kinase D regulates cofilin activity through p21-activated kinase 4. J Biol Chem. 2011;286:34254-61 pubmed publisher..can also regulate LIMK through direct phosphorylation and activation of its upstream kinase p21-activated kinase 4 (PAK4). Therefore, active PKD increases the net amount of phosphorylated inactive cofilin in cells through both pathways...
- Moon S, Kim J, Sung J, Kang M, Kim S, Chang H, et al. p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines. Cancer Res Treat. 2015;47:501-8 pubmed publisher..To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment...
- Pan S, Fei A, Jing L, Zhang X, Gao C. Increased Circulating Endothelial Microparticles Associated with PAK4 Play a Key Role in Ventilation-Induced Lung Injury Process. Biomed Res Int. 2017;2017:4902084 pubmed publisher..VILI inhibited the cytoskeleton-regulating protein of PAK4 and was accompanied by an increased circulating EMP level...
- Wang Z, Zhang X, Yang Z, Du H, Wu Z, Gong J, et al. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells. Biochem Biophys Res Commun. 2012;427:444-9 pubmed publisher..We identified PAK4 as a novel target of miR-145 using informatics screening...
- Xue J, Chen L, Li Z, Hu Y, Yan S, Liu L. MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4). Mol Cell Biochem. 2015;399:77-86 pubmed publisherHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. P21-activated kinase 4 (PAK4) has been identified as an oncogenic protein in a variety of cancers...
- Choi S, Yeon J, Ryu B, Kim K, Moon S, Lee H, et al. Repositioning Potential of PAK4 to Osteoclastic Bone Resorption. J Bone Miner Res. 2015;30:1494-507 pubmed publisher..Here we investigated the possibility of using the anticancer p21-activated kinase 4 (PAK4)-targeted inhibitor PF-3758309 to treat osteoclast-mediated disorders...
- Barry D, Koo Y, Norden P, Wylie L, Xu K, Wichaidit C, et al. Rasip1-Mediated Rho GTPase Signaling Regulates Blood Vessel Tubulogenesis via Nonmuscle Myosin II. Circ Res. 2016;119:810-26 pubmed publisher..depends on Rasip1, as well as the GTPase Cdc42 (cell division control protein 42 homolog) and the kinase Pak4 (serine/threonine-protein kinase 4)...
- Hwang V, Zhou X, Chen X, Trott J, Abu Aboud O, Shim K, et al. Anticystogenic activity of a small molecule PAK4 inhibitor may be a novel treatment for autosomal dominant polycystic kidney disease. Kidney Int. 2017;92:922-933 pubmed publisher..we evaluated the use of an orally bioavailable small molecule, KPT-9274 (a dual inhibitor of the protein kinase PAK4 and nicotinamide phosphoribosyl transferase), for treatment of ADPKD...
- Hao C, Zhao F, Song H, Guo J, Li X, Jiang X, et al. Structure-based design of 6-chloro-4-aminoquinazoline-2-carboxamide derivatives as potent and selective p21-activated kinase 4 (PAK4) inhibitors. J Med Chem. 2017;: pubmed publisherHerein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold...
- Davis S, Sheppard K, Anglesio M, George J, Traficante N, Fereday S, et al. Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition. Mol Cancer Ther. 2015;14:1495-503 pubmed publisher..Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI...
- Hudson A, Yates T, Li Y, Trotter E, Fawdar S, Chapman P, et al. Discrepancies in cancer genomic sequencing highlight opportunities for driver mutation discovery. Cancer Res. 2014;74:6390-6396 pubmed publisher..We demonstrate, using a newly identified PAK4 mutation as proof of principle, that specific targeting and sequencing of these GC-rich cold-spot regions can lead ..
- Ryu B, Kim S, Min B, Kim K, Lee J, Park W, et al. Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor. Cancer Lett. 2014;349:45-50 pubmed publisherFunctional versatility and elevated expression in cancers have endowed p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug target...
- Fulciniti M, Martinez Lopez J, Senapedis W, Oliva S, Lakshmi Bandi R, Amodio N, et al. Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma. Blood. 2017;129:2233-2245 pubmed publisher..Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4) and its potential as a new target in MM for clinical applications...
- Abu Aboud O, Chen C, Senapedis W, Baloglu E, Argueta C, Weiss R. Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. Mol Cancer Ther. 2016;15:2119-29 pubmed publisher..Borrowing from studies on other malignancies, we have identified the PAK4 and NAD biosynthetic pathways as being essential for RCC growth...
- Aboukameel A, Muqbil I, Senapedis W, Baloglu E, Landesman Y, Shacham S, et al. Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma. Mol Cancer Ther. 2017;16:76-87 pubmed publisherThe p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases and is found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells but not in normal human pancreatic ductal epithelia (HPDE)...
- Yuan L, Duan X, Dong J, Lu Q, Zhou J, Zhao Z, et al. p21-Activated Kinase 4 Promotes Intimal Hyperplasia and Vascular Smooth Muscle Cells Proliferation during Superficial Femoral Artery Restenosis after Angioplasty. Biomed Res Int. 2017;2017:5296516 pubmed publisherThe aim of this study is to explore the function of p21-activated kinase 4 (PAK4) in intimal hyperplasia (IH) and vascular smooth muscle cells (VSMCs) proliferation...
- Rane C, Minden A. P21 activated kinase signaling in cancer. Semin Cancer Biol. 2019;54:40-49 pubmed publisher..PAK1 and PAK4, which belong to Group I and Group II PAKs, respectively, are most often associated with tumorigenesis...
- Li Y, Rowland C, Xiromerisiou G, Lagier R, Schrodi S, Dradiotis E, et al. Neither replication nor simulation supports a role for the axon guidance pathway in the genetics of Parkinson's disease. PLoS ONE. 2008;3:e2707 pubmed publisher..Together, these results challenge the robustness of the reported panel of genetic markers to predict PD risk in particular and a role of the axon guidance pathway in PD genetics in general. ..
- Norden P, Kim D, Barry D, CLEAVER O, Davis G. Cdc42 and k-Ras Control Endothelial Tubulogenesis through Apical Membrane and Cytoskeletal Polarization: Novel Stimulatory Roles for GTPase Effectors, the Small GTPases, Rac2 and Rap1b, and Inhibitory Influence of Arhgap31 and Rasa1. PLoS ONE. 2016;11:e0147758 pubmed publisher..has been obtained concerning these issues, including the role of Cdc42 and Rac1 and their effectors such as Pak2, Pak4, Par6b, and co-regulators such as integrins, MT1-MMP and Par3; many key questions remain that are necessary to ..
- Gringel A, Walz D, Rosenberger G, Minden A, Kutsche K, Kopp P, et al. PAK4 and alphaPIX determine podosome size and number in macrophages through localized actin regulation. J Cell Physiol. 2006;209:568-79 pubmed..Here, we show that the RhoGTPase effector PAK4, a member of the p21 associated kinase family, and its regulator alphaPIX (PAK-interacting exchange factor), are ..
- Dart A, Wells C. P21-activated kinase 4--not just one of the PAK. Eur J Cell Biol. 2013;92:129-38 pubmed publisherP21-activated kinase 4 (PAK4) is a member of the p21-activated kinase (PAK) family. Historically much of the attention has been directed towards founding family member PAK1 but the focus is now shifting towards PAK4...
- Guo Q, Su N, Zhang J, Li X, Miao Z, Wang G, et al. PAK4 kinase-mediated SCG10 phosphorylation involved in gastric cancer metastasis. Oncogene. 2014;33:3277-87 pubmed publisher..In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regulates MT homeostasis in metastatic gastric cancer...
- Jin D, Durgan J, Hall A. Functional cross-talk between Cdc42 and two downstream targets, Par6B and PAK4. Biochem J. 2015;467:293-302 pubmed publisher..Two Cdc42 target proteins, the kinase PAK4 [p21 protein (Cdc42/Rac)-activated kinase 4] and the scaffold partitioning defective (Par) 6B, are required to ..
- Hao C, Huang W, Li X, Guo J, Chen M, Yan Z, et al. Development of 2, 4-diaminoquinazoline derivatives as potent PAK4 inhibitors by the core refinement strategy. Eur J Med Chem. 2017;131:1-13 pubmed publisherUpon analysis of the reported crystal structure of PAK4 inhibitor KY04031 (PAK4 IC50 = 0.790 ?M) in the active site of PAK4, we investigated the possibility of changing the triazine core of KY04031 to a quinazoline...
- Kim H, Woo D, Kim S, Yang E. p21-activated kinase 4 regulates HIF-1? translation in cancer cells. Biochem Biophys Res Commun. 2017;486:270-276 pubmed publisher..In this study, we found that both Pak1 and Pak4 are highly expressed in HeLa cervical cancer cells, but only Pak4 knockdown attenuates expression of hypoxia-..
- Ha B, Boggon T. CDC42 binds PAK4 via an extended GTPase-effector interface. Proc Natl Acad Sci U S A. 2018;115:531-536 pubmed publisher..Here we probe the interaction of the type II PAK, PAK4, with RHO GTPases...
- Tyagi N, Bhardwaj A, Singh A, McClellan S, Carter J, Singh S. p-21 activated kinase 4 promotes proliferation and survival of pancreatic cancer cells through AKT- and ERK-dependent activation of NF-κB pathway. Oncotarget. 2014;5:8778-89 pubmed..Here, we investigated the expression and pathobiological significance of p21-activated kinase 4 (PAK4), a gene that was earlier shown to be amplified in a sub-set of PC...
- Yi K, Kim S, Ihm H, Oh Y, Chae H, Kim C, et al. Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells. Fertil Steril. 2015;103:1089-1097.e2 pubmed publisherTo investigate the expression of p21-activated kinase 4 (Pak4) in both adenomyotic foci and the eutopic endometrium of women with adenomyosis, and whether the activities of matrix metalloproteinases (MMPs)-2 and -9 are regulated by Pak4 ..
- Song B, Wang W, Zheng Y, Yang J, Xu Z. P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration. J Surg Res. 2015;196:130-5 pubmed publisher..The aim of this study was to investigate the relationship between PAK1 and PAK4 and clinicopathologic features of colorectal cancer...
- Tabanifar B, Zhao Z, Manser E. PAK5 is auto-activated by a central domain that promotes kinase oligomerization. Biochem J. 2016;473:1777-89 pubmed publisher..The group II kinases PAK4 and PAK5 are considered significant therapeutic targets in cancer...
- Hao C, Li X, Song S, Guo B, Guo J, Zhang J, et al. Advances in the 1-phenanthryl-tetrahydroisoquinoline series of PAK4 inhibitors: potent agents restrain tumor cell growth and invasion. Org Biomol Chem. 2016;14:7676-90 pubmed publisher..1-phenanthryl-tetrahydroisoquinoline derivatives were designed, synthesized and biologically evaluated for their PAK4 inhibitory activities and anti-proliferative effects against three cancer cell lines A549, MCF-7 and HT-1080...
- Edlinger L, Berger Becvar A, Menzl I, Hoermann G, Greiner G, Grundschober E, et al. Expansion of BCR/ABL1+ cells requires PAK2 but not PAK1. Br J Haematol. 2017;179:229-241 pubmed publisher..To date, PAK deregulation has mainly been studied in solid tumours, where PAK1 and PAK4 are the main isoforms deregulated...
- Chaker M, Minden A, Chen S, Weiss R, Chini E, Mahipal A, et al. Rho GTPase effectors and NAD metabolism in cancer immune suppression. Expert Opin Ther Targets. 2017;: pubmed publisher..Areas covered: We review the emerging roles of GTPase effector proteins particularly the p21 activated kinase 4 (PAK4) and nicotinamide biosynthetic pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) as signaling molecules ..
- Barac A, Basile J, Vazquez Prado J, Gao Y, Zheng Y, Gutkind J. Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor. J Biol Chem. 2004;279:6182-9 pubmed..to Rho activation, binds through its C-terminal region to the serine-threonine kinase p21-activated kinase 4 (PAK4), an effector for Cdc42...
- Wells C, Jones G. The emerging importance of group II PAKs. Biochem J. 2010;425:465-73 pubmed publisher..There are six mammalian PAKs that can be divided into two groups: group I PAKs (PAK1-3) and group II PAKs (PAK4-6)...
- Wu T, Pang Y, Guo J, Yin W, Zhu M, Hao C, et al. Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-quinazoline-2,4-diamines as PAK4 Inhibitors with Potent A549 Cell Proliferation, Migration, and Invasion Inhibition Activity. Molecules. 2018;23: pubmed publisher..of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4) inhibitors...
- Kobayashi K, Inokuchi M, Takagi Y, Otsuki S, Fujimori Y, Sato Y, et al. Prognostic significance of PAK4 expression in gastric cancer. J Clin Pathol. 2016;69:580-5 pubmed publisher..However, the clinical significance of PAK4 in gastric cancer has yet to be fully elucidated...
- Sheng N, Tan G, You W, Chen H, Gong J, Chen D, et al. MiR-145 inhibits human colorectal cancer cell migration and invasion via PAK4-dependent pathway. Cancer Med. 2017;6:1331-1340 pubmed publisher..Here, we reported an intense correlation between the expressions of PAK4 and miR-145 in human CRC cell lines...
- Kesanakurti D, Maddirela D, Banasavadi Siddegowda Y, Lai T, Qamri Z, Jacob N, et al. A novel interaction of PAK4 with PPARγ to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma. Oncogene. 2017;36:5309-5320 pubmed publisher..We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance...
- Su T, Qu J, Wang K, Li B, Zhao D, Zhu Y, et al. Cross-talk between p21-activated kinase 4 and ER? signaling triggers endometrial cancer cell proliferation. Oncotarget. 2017;8:68083-68094 pubmed publisher..Here, we show that 17?-estradiol (E2) stimulation increases p21-activated kinase 4 (Pak4) expression and activation in ER-positive EC cells...
- Ha U, Lim J, Kim H, Wu W, Jin S, Xu H, et al. MKP1 regulates the induction of MUC5AC mucin by Streptococcus pneumoniae pneumolysin by inhibiting the PAK4-JNK signaling pathway. J Biol Chem. 2008;283:30624-31 pubmed publisher..Here we show that the PAK4-JNK signaling pathway acted as a negative regulator for Streptococcus pneumoniae pneumolysin-induced MUC5AC mucin ..
- Wong L, Reynolds A, Dissanayaka N, Minden A. p120-catenin is a binding partner and substrate for Group B Pak kinases. J Cell Biochem. 2010;110:1244-54 pubmed publisher..Both Pak5 and constitutively active Pak4, the founding member of the Group B Paks, directly phosphorylate p120 in vitro...
- Bompard G, Rabeharivelo G, Cau J, Abrieu A, Delsert C, Morin N. P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring. Oncogene. 2013;32:910-9 pubmed publisherThe oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2/M transition of the cell cycle. We have also identified that PAK4 regulates Ran GTPase activity during mitosis...
- Sanlorenzo M, Vujic I, Posch C, Ma J, Lin K, Lai K, et al. Oncogenic KIT mutations in different exons lead to specific changes in melanocyte phospho-proteome. J Proteomics. 2016;144:140-7 pubmed publisher..We concluded that CK1 ? and ? are more active in cell clones harboring KIT(559) and KIT(642) mutations, whereas PAK4 is more active in clones with KIT(816) mutation...
- Won S, Park M, You S, Choi S, Kim H, McLean C, et al. Nigral dopaminergic PAK4 prevents neurodegeneration in rat models of Parkinson's disease. Sci Transl Med. 2016;8:367ra170 pubmed..We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons...
- Zhao M, Rabieifar P, Costa T, Zhuang T, Minden A, Lohr M, et al. Pdx1-Cre-driven conditional gene depletion suggests PAK4 as dispensable for mouse pancreas development. Sci Rep. 2017;7:7031 pubmed publisherConstitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes embryonic lethality associated with heart and brain defects...
- Mao K, Lei D, Zhang H, You C. MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4. Int J Oncol. 2017;51:1521-1532 pubmed publisher..In addition, p21?activated kinase 4 (PAK4) was demonstrated to be a direct and functional target of miR?485 in GBM...
- Li Z, Li X, Xu L, Tao Y, Yang C, Chen X, et al. Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017;38:2705-2716 pubmed publisher..p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and ..
- Begum A, Imoto I, Kozaki K, Tsuda H, Suzuki E, Amagasa T, et al. Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma. Cancer Sci. 2009;100:1908-16 pubmed publisher..and expression level-dependent proliferation-promoting activity led us to conclude that the p21-activated kinase 4 (PAK4) gene was the most likely target...
- Yu F, Zhang X, Wang Y, Ma N, Du H, Ma J, et al. Gene polymorphisms of interleukin-28, p21-activated protein kinases 4, and response to interferon-? based therapy in Chinese patients with chronic hepatitis B. Chin Med J (Engl). 2013;126:1726-31 pubmed..assess the relationship between the gene polymorphisms of interleukin-28 (IL-28), p21-activated protein kinase 4 (PAK4) and the response to interferon treatment in chronic hepatitis B patients...
- Li D, Zhang Y, Li Z, Wang X, Qu X, Liu Y. Activated Pak4 expression correlates with poor prognosis in human gastric cancer patients. Tumour Biol. 2015;36:9431-6 pubmed publisher..P21-activated serine/threonine kinase 4 (Pak4) plays an important role in cell morphology and cytoskeletal reorganization-both prerequisite steps for cell ..
- Baskaran Y, Ang K, Anekal P, Chan W, Grimes J, Manser E, et al. An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nat Commun. 2015;6:8681 pubmed publisherb>PAK4 is a metazoan-specific kinase acting downstream of Cdc42. Here we describe the structure of human PAK4 in complex with Inka1, a potent endogenous kinase inhibitor...
- Zhao M, Spiess M, Johansson H, Olofsson H, Hu J, Lehtiö J, et al. Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization. Oncotarget. 2017;8:77061-77074 pubmed publisherp21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed...
- Kim T, Kang Y, Park Z, Kim Y, Hong S, Oh S, et al. SH3RF2 functions as an oncogene by mediating PAK4 protein stability. Carcinogenesis. 2014;35:624-34 pubmed publisher..that SH3RF2 is an oncogene product that is overexpressed in human cancers and regulates p21-activated kinase 4 (PAK4) protein stability...
- Nicholas N, Pipili A, Lesjak M, Ameer Beg S, Geh J, Healy C, et al. PAK4 suppresses PDZ-RhoGEF activity to drive invadopodia maturation in melanoma cells. Oncotarget. 2016;7:70881-70897 pubmed publisher..and disassembly role for Rho family effector p-21 activated kinase 1 (PAK1) however, related family member PAK4 has not been explored...
- Fu X, Feng J, Zeng D, Ding Y, Yu C, Yang B. PAK4 confers cisplatin resistance in gastric cancer cells via PI3K/Akt- and MEK/ERK-dependent pathways. Biosci Rep. 2014;34: pubmed..However, CDDP efficiency is limited because of development of drug resistance. In this study, we found that PAK4 (p21-activated kinase 4) expression and activity were elevated in gastric cancer cells with acquired CDDP ..
- Baskaran Y, Ng Y, Selamat W, Ling F, Manser E. Group I and II mammalian PAKs have different modes of activation by Cdc42. EMBO Rep. 2012;13:653-9 pubmed publisher..They are subdivided into PAK1-like (group I) or PAK4-like (group II) kinases. Human PAK4 is widely expressed and its regulatory mechanism is unknown...
- Ryu B, Lee H, Kim S, Heo J, Choi S, Yeon J, et al. 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. Mol Cell Biochem. 2014;389:69-77 pubmed publisher..PF-3758309 suppresses CREB, NF-?B, and ?-catenin pathways, which are well known to be closely related with cell migration. This leads to the downregulation of MMP-2/MMP-9 expressions and the inhibition of A549 lung cancer metastasis. ..