PAK4

Summary

Gene 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

  1. Wang C, Li Y, Zhang H, Liu F, Cheng Z, Wang D, et al. Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis. Oncogene. 2014;33:3473-84 pubmed publisher
    The alteration of p21-activated kinase 4 (PAK4) and transforming growth factor-beta (TGF-?) signaling effector Smad2/3 was detected in several types of tumors, which acts as oncogenic factor and tumor suppressor, but the relationship ..
  2. Tabusa H, Brooks T, Massey A. Knockdown of PAK4 or PAK1 inhibits the proliferation of mutant KRAS colon cancer cells independently of RAF/MEK/ERK and PI3K/AKT signaling. Mol Cancer Res. 2013;11:109-21 pubmed publisher
    ..Knockdown of PAK4 or PAK1 inhibited the proliferation of mutant KRAS or BRAF colon cancer cells in vitro...
  3. Ha B, Davis M, Chen C, Lou H, Gao J, Zhang R, et al. Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate. Proc Natl Acad Sci U S A. 2012;109:16107-12 pubmed publisher
    ..We determined six X-ray crystal structures of either full-length PAK4 or its catalytic domain, that demonstrate the molecular basis for pseudosubstrate binding to the active state with ..
  4. Zhang J, Wang J, Guo Q, Wang Y, Zhou Y, Peng H, et al. LCH-7749944, a novel and potent p21-activated kinase 4 inhibitor, suppresses proliferation and invasion in human gastric cancer cells. Cancer Lett. 2012;317:24-32 pubmed publisher
    P21-activated kinase 4 (PAK4), a serine/threonine protein kinase, has involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion...
  5. Mak G, Chan M, Leong V, Lee J, Yau T, Ng I, et al. Overexpression of a novel activator of PAK4, the CDK5 kinase-associated protein CDK5RAP3, promotes hepatocellular carcinoma metastasis. Cancer Res. 2011;71:2949-58 pubmed publisher
    ..We found that overexpression of CDK5RAP3 and p21-activated protein kinase 4 (PAK4) correlated in human HCCs, and that CDK5RAP3 was a novel binding partner of PAK4, and this binding enhanced PAK4 ..
  6. Kimmelman A, Hezel A, Aguirre A, Zheng H, Paik J, Ying H, et al. Genomic alterations link Rho family of GTPases to the highly invasive phenotype of pancreas cancer. Proc Natl Acad Sci U S A. 2008;105:19372-7 pubmed publisher
    ..prompted a genome wide survey of other components of the Rho family network, revealing p21 Activated Kinase 4 (PAK4) as another amplified gene in PDAC tumors and cell lines...
  7. Bagrodia S, Cerione R. Pak to the future. Trends Cell Biol. 1999;9:350-5 pubmed
    ..We present these recent findings and consider how these new regulators and targets could explain some of the cellular effects that have been attributed to Pak family members. ..
  8. Abo A, Qu J, Cammarano M, Dan C, Fritsch A, Baud V, et al. PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia. EMBO J. 1998;17:6527-40 pubmed
    ..We have identified a novel PAK-related kinase, PAK4, as a new effector molecule for Cdc42Hs...
  9. 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 ..

More Information

Publications97

  1. Zhang H, Li Z, Viklund E, Stromblad S. P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration. J Cell Biol. 2002;158:1287-97 pubmed
    ..de Lanerolle. 1999. SCIENCE: 283:2083-2085). We here present a novel cell motility pathway by demonstrating that PAK4 directly interacts with an integrin intracellular domain and regulates carcinoma cell motility in an integrin-..
  2. 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...
  3. 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 ..
  4. 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 publisher
    The 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 ..
  5. 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...
  6. 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)..
  7. 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...
  8. 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...
  9. 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...
  10. 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 publisher
    Overexpression, 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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 pubmed
    b>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...
  15. 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...
  16. 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...
  17. 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 pubmed
    b>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...
  18. 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...
  19. 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 publisher
    Hepatocellular 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...
  20. 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 publisher
    Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold...
  21. 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...
  22. 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)...
  23. 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...
  24. 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...
  25. 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 ..
  26. 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...
  27. 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...
  28. 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 publisher
    Functional versatility and elevated expression in cancers have endowed p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug target...
  29. 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...
  30. 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 publisher
    The 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...
  31. Rane C, Minden A. P21 activated kinase signaling in cancer. Semin Cancer Biol. 2018;: pubmed publisher
    ..PAK1 and PAK4, which belong to Group I and Group II PAKs, respectively, are most often associated with tumorigenesis...
  32. 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 publisher
    The 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)...
  33. 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...
  34. 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 ..
  35. Cosset Ã, 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...
  36. 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. ..
  37. 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...
  38. 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 publisher
    Upon 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...
  39. 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 ..
  40. 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...
  41. 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 ..
  42. 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-..
  43. Dart A, Wells C. P21-activated kinase 4--not just one of the PAK. Eur J Cell Biol. 2013;92:129-38 pubmed publisher
    P21-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...
  44. 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...
  45. 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 publisher
    To 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 ..
  46. 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...
  47. 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...
  48. 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 ..
  49. 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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)...
  54. Williamson R, Cowell C, Hammond C, Bergen D, Roper J, Feng Y, et al. Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure. J Cell Sci. 2014;127:4292-307 pubmed publisher
  55. 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...
  56. 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...
  57. 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...
  58. 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...
  59. 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...
  60. 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 ..
  61. 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...
  62. 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 ..
  63. 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...
  64. 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 publisher
    Constitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes embryonic lethality associated with heart and brain defects...
  65. 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 publisher
    The 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...
  66. 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...
  67. 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 publisher
    b>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...
  68. 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...
  69. 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...
  70. 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 publisher
    p21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed...
  71. 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 ..
  72. 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...
  73. 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 ..
  74. 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...
  75. 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. ..
  76. Bhardwaj A, Srivastava S, Singh S, Arora S, Tyagi N, Andrews J, et al. CXCL12/CXCR4 signaling counteracts docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIM domain kinase 1. Oncotarget. 2014;5:11490-500 pubmed
    ..studies, we show that the chemoprotective action of CXCL12/CXCR4 signaling is mediated by p21-activated kinase 4 (PAK4)-dependent activation of Lim domain kinase 1 (LIMK1), and inhibition of either PAK4 or LIMK1 leads to re-..
  77. He L, Xu H, Chen M, Xian Z, Wen X, Chen M, et al. Activated-PAK4 predicts worse prognosis in breast cancer and promotes tumorigenesis through activation of PI3K/AKT signaling. Oncotarget. 2017;8:17573-17585 pubmed publisher
    The p21-activated kinase 4 (PAK4) is sufficient to transform noncancerous mammary epithelial cells and to form tumors in the mammary glands of mice...
  78. Xie X, Shi X, Guan H, Guo Q, Fan C, Dong W, et al. P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation. Oncotarget. 2017;8:24882-24891 pubmed publisher
    Papillary thyroid cancer is a common endocrine malignancy. Although p21-activated kinase 4 (PAK4) is involved in the development of different types of tumor, its function has not been investigated in papillary thyroid cancer...
  79. 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...
  80. Miura K, Nojiri T, Akitake Y, Ando K, Fukuhara S, Zenitani M, et al. CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote cell spreading. Biochem J. 2017;474:1897-1918 pubmed publisher
    ..p21-activated kinase 4 (PAK4) and cerebral cavernous malformations 2 (CCM2), a scaffold protein involved in a cerebrovascular disease, were ..
  81. Zhang E, Ha B, Boggon T. PAK4 crystal structures suggest unusual kinase conformational movements. Biochim Biophys Acta Proteins Proteom. 2018;1866:356-365 pubmed publisher
    ..We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077)...
  82. Cai S, Ye Z, Wang X, Pan Y, Weng Y, Lao S, et al. Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion. J Exp Clin Cancer Res. 2015;34:48 pubmed publisher
    P21-activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is an important oncogene whose expression is increased in many human cancers and is generally positively correlated with advanced disease and decreased survival...
  83. Guo J, Zhu M, Wu T, Hao C, Wang K, Yan Z, et al. Discovery of indolin-2-one derivatives as potent PAK4 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study. Bioorg Med Chem. 2017;25:3500-3511 pubmed publisher
    ..Compounds 11b, 12d and 12g exhibited the most potent inhibitory activity against PAK4 (IC50=22nM, 16nM and 27nM, respectively)...
  84. Tyagi N, Marimuthu S, Bhardwaj A, Deshmukh S, Srivastava S, Singh A, et al. p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling. Cancer Lett. 2016;370:260-7 pubmed publisher
    ..Here we investigated the role of p-21 activated kinase 4 (PAK4) in driving PC stemness properties...
  85. Rane C, Patel M, Cai L, Senapedis W, Baloglu E, Minden A. Decrypting the PAK4 transcriptome profile in mammary tumor forming cells using Next Generation Sequencing. Genomics. 2017;: pubmed publisher
    The p-21 Activated Kinase 4 (PAK4) protein kinase is implicated in many cancers, including breast cancer. Overexpression of PAK4 is sufficient to cause mouse mammary epithelial cells (iMMECs) to become tumorigenic...
  86. Wallace S, Durgan J, Jin D, Hall A. Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B. Mol Biol Cell. 2010;21:2996-3006 pubmed publisher
    ..Two targets, PAK4 and Par6B, were identified as necessary for the formation of apical junctions...
  87. Vershinin Z, Feldman M, Chen A, Levy D. PAK4 Methylation by SETD6 Promotes the Activation of the Wnt/β-Catenin Pathway. J Biol Chem. 2016;291:6786-95 pubmed publisher
    ..We have identified the p21-activated kinase 4 (PAK4) as a new substrate for methylation by the protein lysine methyltransferase SETD6...
  88. Lu W, Xia Y, Qu J, He Y, Li B, Lu C, et al. p21-activated kinase 4 regulation of endometrial cancer cell migration and invasion involves the ERK1/2 pathway mediated MMP-2 secretion. Neoplasma. 2013;60:493-503 pubmed publisher
    ..So far, however, the underlying molecular mechanisms of EC metastasis are largely unknown. P21-activated kinase 4 (Pak4) is important in cell motility and oncogenesis...