PAK1

Summary

Gene Symbol: PAK1
Description: p21 (RAC1) activated kinase 1
Alias: PAKalpha, serine/threonine-protein kinase PAK 1, STE20 homolog, yeast, alpha-PAK, p21 protein (Cdc42/Rac)-activated kinase 1, p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast), p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related), p65-PAK
Species: human
Products:     PAK1

Top Publications

  1. Rhee S, Grinnell F. P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts. J Cell Biol. 2006;172:423-32 pubmed
    ..show that the PDGF and LPA signaling pathways required for matrix contraction converge on p21-activated kinase 1 (PAK1) and its downstream effector cofilin1 and that contraction depends on cellular ruffling activity, rather than on ..
  2. Liu F, Li X, Wang C, Cai X, Du Z, Xu H, et al. Downregulation of p21-activated kinase-1 inhibits the growth of gastric cancer cells involving cyclin B1. Int J Cancer. 2009;125:2511-9 pubmed publisher
    p21-Activated kinase 1 (Pak1), a serine/threonine kinase, has been implicated in cytoskeletal remodelling, cell motility, apoptosis and transformation. However, the role of Pak1 in gastric cancer remains unclear...
  3. Jaffer Z, Chernoff J. p21-activated kinases: three more join the Pak. Int J Biochem Cell Biol. 2002;34:713-7 pubmed
    ..The Group I Paks (Pak1, Pak2, Pak3) have been studied in greater detail and shown to be involved in the regulation of cellular processes ..
  4. Huynh N, Liu K, Baldwin G, He H. P21-activated kinase 1 stimulates colon cancer cell growth and migration/invasion via ERK- and AKT-dependent pathways. Biochim Biophys Acta. 2010;1803:1106-13 pubmed publisher
    ..b>PAK1 promotes transformation through facilitating the ERK/MAPK pathway and enhances cell migration and survival by ..
  5. He H, Huynh N, Liu K, Malcontenti Wilson C, Zhu J, Christophi C, et al. P-21 activated kinase 1 knockdown inhibits ?-catenin signalling and blocks colorectal cancer growth. Cancer Lett. 2012;317:65-71 pubmed publisher
    The p21-activated kinase 1 (PAK1) plays important roles in cell growth, motility, and transformation...
  6. Schurmann A, Mooney A, Sanders L, Sells M, Wang H, Reed J, et al. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Mol Cell Biol. 2000;20:453-61 pubmed
    ..p21-activated kinase 1 (PAK1) is activated by IL-3 in FL5...
  7. Adam L, Vadlamudi R, Kondapaka S, Chernoff J, Mendelsohn J, Kumar R. Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase. J Biol Chem. 1998;273:28238-46 pubmed
    ..In addition, HRG triggered a rapid stimulation of p21-activated kinase1 (PAK1) activity and its redistribution into the leading edges of motile cells...
  8. Delorme V, Machacek M, DerMardirossian C, Anderson K, Wittmann T, Hanein D, et al. Cofilin activity downstream of Pak1 regulates cell protrusion efficiency by organizing lamellipodium and lamella actin networks. Dev Cell. 2007;13:646-62 pubmed
    ..fluorescent speckle microscopy, immunofluorescence, and electron microscopy, we establish that the Rac1/Pak1/LIMK1 signaling pathway controls cofilin activity within the lamellipodium...
  9. Singh R, Song C, Yang Z, Kumar R. Nuclear localization and chromatin targets of p21-activated kinase 1. J Biol Chem. 2005;280:18130-7 pubmed
    b>Pak1 (p21-activated kinase 1), a conserved, mammalian signaling kinase, is a downstream effector of small GTPases Rac1 and Cdc42 and of growth factor signaling...

More Information

Publications100

  1. Manser E, Huang H, Loo T, Chen X, Dong J, Leung T, et al. Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol. 1997;17:1129-43 pubmed
    ..These data support our previous suggestions of a role for PAK downstream of both Cdc42 and Rac1 and indicate that PAK functions include the dissolution of stress fibers and reorganization of focal complexes. ..
  2. Chen S, Yin X, Zhu X, Yan J, Ji S, Chen C, et al. The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis. J Biol Chem. 2003;278:20029-36 pubmed
    ..used the yeast two-hybrid system to screen a human fetal liver cDNA library and identified p21-activated kinase 1 (PAK1) as an interacting partner of p110C...
  3. Menard R, Jovanovski A, Mattingly R. Active p21-activated kinase 1 rescues MCF10A breast epithelial cells from undergoing anoikis. Neoplasia. 2005;7:638-45 pubmed
    The protein kinase, PAK1, is overexpressed in human breast cancer and may contribute to malignancy through induction of proliferation and invasiveness...
  4. Carter J, Douglass L, Deddens J, Colligan B, Bhatt T, Pemberton J, et al. Pak-1 expression increases with progression of colorectal carcinomas to metastasis. Clin Cancer Res. 2004;10:3448-56 pubmed
    ..These data, along with numerous functional studies demonstrating a central role for Pak-1 activity in tumor invasiveness and motility, implicate Pak-1 as an exciting target for therapy of colorectal carcinoma. ..
  5. Ong C, Jubb A, Zhou W, Haverty P, Harris A, Belvin M, et al. p21-activated kinase 1: PAK'ed with potential. Oncotarget. 2011;2:491-6 pubmed
    ..In this perspective, we summarize recent data concerning the contribution of the PAK family member, PAK1, in growth factor signaling and tumorigenesis...
  6. Park M, Kim D, You S, Lee C, Kim H, Park S, et al. Phosphorylation of ?-catenin at serine 663 regulates its transcriptional activity. Biochem Biophys Res Commun. 2012;419:543-9 pubmed publisher
    ..cellular function, and serine 675 (S675) was previously identified as a common target of p21-activated kinase 1 (PAK1) and protein kinase A. In the present study, we explored the PAK1-specific phosphorylation site(s) in ?-catenin...
  7. Wiskerchen M, Cheng Mayer C. HIV-1 Nef association with cellular serine kinase correlates with enhanced virion infectivity and efficient proviral DNA synthesis. Virology. 1996;224:292-301 pubmed
  8. Vadlamudi R, Bagheri Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin A, et al. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004;5:575-85 pubmed
    We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88...
  9. DerMardirossian C, Schnelzer A, Bokoch G. Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol Cell. 2004;15:117-27 pubmed
    ..We identified a RhoGDI kinase from bovine brain as p21-activated kinase (Pak). Pak1 binds and phosphorylates RhoGDI both in vitro and in vivo at Ser101 and Ser174...
  10. Lightcap C, Kari G, Arias Romero L, Chernoff J, Rodeck U, Williams J. Interaction with LC8 is required for Pak1 nuclear import and is indispensable for zebrafish development. PLoS ONE. 2009;4:e6025 pubmed publisher
    b>Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells...
  11. Rashid T, Banerjee M, Nikolic M. Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology. J Biol Chem. 2001;276:49043-52 pubmed
    The small GTPase Rac and its effectors, the Pak1 and p35/Cdk5 kinases, have been assigned important roles in regulating cytoskeletal dynamics in neurons...
  12. Weber D, Taniyama Y, Rocic P, Seshiah P, Dechert M, Gerthoffer W, et al. Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration. Circ Res. 2004;94:1219-26 pubmed
    ..kinase-1 [PDK1] site) was attenuated by ROS inhibition, and infection of VSMCs with dominant-negative PAK1 adenovirus attenuated migration...
  13. Zhao Z, Manser E, Chen X, Chong C, Leung T, Lim L. A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1. Mol Cell Biol. 1998;18:2153-63 pubmed
    ..These results, coupled with previous observations with constitutively active PAK, demonstrate that these kinases play an important role downstream of Cdc42 and Rac1 in cytoskeletal reorganization. ..
  14. Kissil J, Wilker E, Johnson K, Eckman M, Yaffe M, Jacks T. Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell. 2003;12:841-9 pubmed
    ..We describe a novel interaction between merlin and p21-activated kinase 1 (Pak1), which is dynamic and facilitated upon increased cellular confluence...
  15. Kamai T, Shirataki H, Nakanishi K, Furuya N, Kambara T, Abe H, et al. Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer. BMC Cancer. 2010;10:164 pubmed publisher
    ..We analyzed Rac1 activity and Pak1 protein expression in matched sets of tumor tissue, non-tumor tissue, and metastatic lymph node tissue obtained ..
  16. Rayala S, Talukder A, Balasenthil S, Tharakan R, Barnes C, Wang R, et al. P21-activated kinase 1 regulation of estrogen receptor-alpha activation involves serine 305 activation linked with serine 118 phosphorylation. Cancer Res. 2006;66:1694-701 pubmed
    Here, we investigated the role of P21-activated kinase 1 (Pak1) signaling in the function of estrogen receptor-alpha (ER-alpha) as assessed by serine 305 (S305) activation and transactivation activity of ER...
  17. Kraynov V, Chamberlain C, Bokoch G, Schwartz M, Slabaugh S, Hahn K. Localized Rac activation dynamics visualized in living cells. Science. 2000;290:333-7 pubmed
    ..FLAIR exemplifies a generally applicable approach for examining spatio-temporal control of protein activity. ..
  18. Coles L, Shaw P. PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway. Oncogene. 2002;21:2236-44 pubmed
    ..Here we show that both Raf-1 and MEK1 are phosphorylated by PAK1 and that mutations at PAK1 phosphorylation sites in either protein prevent cross-cascade activation...
  19. Balasenthil S, Sahin A, Barnes C, Wang R, Pestell R, Vadlamudi R, et al. p21-activated kinase-1 signaling mediates cyclin D1 expression in mammary epithelial and cancer cells. J Biol Chem. 2004;279:1422-8 pubmed
    p21-activated kinase 1 (Pak1) has been shown recently to induce hyperplasia in the mammary epithelium, a phenotype also manifested by overexpression of cyclin D1, a known indicator of the proliferative stage...
  20. Bostner J, Ahnström Waltersson M, Fornander T, Skoog L, Nordenskjold B, Stal O. Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer. Oncogene. 2007;26:6997-7005 pubmed
    ..Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene...
  21. Sells M, Boyd J, Chernoff J. p21-activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts. J Cell Biol. 1999;145:837-49 pubmed
    The p21 (Cdc42/Rac) activated kinase Pak1 regulates cell morphology and polarity in most, if not all, eukaryotic cells...
  22. Wolf D, Witte V, Laffert B, Blume K, Stromer E, Trapp S, et al. HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals. Nat Med. 2001;7:1217-24 pubmed
    ..Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis. ..
  23. Witte V, Laffert B, Rosorius O, Lischka P, Blume K, Galler G, et al. HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane. Mol Cell. 2004;13:179-90 pubmed
    ..Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism...
  24. Zenke F, King C, Bohl B, Bokoch G. Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity. J Biol Chem. 1999;274:32565-73 pubmed
    ..We present biochemical evidence that an autoinhibitory domain (ID) contained within amino acid residues 67-150 of Pak1 interacts with the carboxyl-terminal kinase domain and that this interaction is regulated in a GTPase-dependent ..
  25. Dharmawardhane S, Sanders L, Martin S, Daniels R, Bokoch G. Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. J Cell Biol. 1997;138:1265-78 pubmed
    ..We have examined the subcellular localization of endogenous PAK1 in fibroblast cell lines using specific PAK1 antibodies...
  26. Frost J, Steen H, Shapiro P, Lewis T, Ahn N, Shaw P, et al. Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins. EMBO J. 1997;16:6426-38 pubmed
    ..Rho family proteins utilize PAKs for this effect, as expression of an active PAK1 mutant can substitute for Rho family small G proteins, and expression of an interfering PAK1 mutant blocks Rho-type ..
  27. Vadlamudi R, Li F, Adam L, Nguyen D, Ohta Y, Stossel T, et al. Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. Nat Cell Biol. 2002;4:681-90 pubmed
    The serine/threonine kinase p21-activated kinase 1 (Pak1) controls the actin cytoskeletal and ruffle formation through mechanisms that are independent of GTPase activity...
  28. Sells M, Knaus U, Bagrodia S, Ambrose D, Bokoch G, Chernoff J. Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol. 1997;7:202-10 pubmed
    ..Here, we report that the microinjection of activated Pak1 protein into quiescent Swiss 3T3 cells induces the rapid formation of polarized filopodia and membrane ruffles...
  29. Zhao Z, Manser E, Lim L. Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation. Mol Cell Biol. 2000;20:3906-17 pubmed
    ..One cellular consequence of the regulatable binding of PAK is facilitation of its cycling between cytosolic and focal complex sites. ..
  30. Vidal C, Geny B, Melle J, Jandrot Perrus M, Fontenay Roupie M. Cdc42/Rac1-dependent activation of the p21-activated kinase (PAK) regulates human platelet lamellipodia spreading: implication of the cortical-actin binding protein cortactin. Blood. 2002;100:4462-9 pubmed
    ..These results suggest that Cdc42/Rac1-dependent activation of PAK may trigger early platelet shape change, at least in part through the regulation of cortactin binding to PAK. ..
  31. Martin G, Bollag G, McCormick F, Abo A. A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. EMBO J. 1995;14:1970-8 pubmed
    ..These data are consistent with a model in which hPAK65 functions as an effector molecule for rac1 and CDC42Hs. ..
  32. Wu Y, Frey D, Lungu O, Jaehrig A, Schlichting I, Kuhlman B, et al. A genetically encoded photoactivatable Rac controls the motility of living cells. Nature. 2009;461:104-8 pubmed publisher
    ..A PA-Rac crystal structure and modelling revealed LOV-Rac interactions that will facilitate extension of this photoactivation approach to other proteins...
  33. Brown J, Stowers L, Baer M, Trejo J, Coughlin S, Chant J. Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway. Curr Biol. 1996;6:598-605 pubmed
    ..Thus, PAK and Ste20 kinases play key parts in linking extracellular signals from membrane components, such as receptor-associated G proteins and Rho-related GTPases, to nuclear responses, such as transcriptional activation. ..
  34. Gatti A, Huang Z, Tuazon P, Traugh J. Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a function of activation. J Biol Chem. 1999;274:8022-8 pubmed
    ..Further, the phosphorylation of Ser-141, Ser-165, and Thr-402 was found to correlate with gamma-PAK activation. ..
  35. Bokoch G, Wang Y, Bohl B, Sells M, Quilliam L, Knaus U. Interaction of the Nck adapter protein with p21-activated kinase (PAK1). J Biol Chem. 1996;271:25746-9 pubmed
    ..We describe here a specific interaction of the Nck adapter molecule with PAK1 both in vitro and in vivo...
  36. Lei M, Lu W, Meng W, Parrini M, Eck M, Mayer B, et al. Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell. 2000;102:387-97 pubmed
    ..crystal structure of a complex between the N-terminal autoregulatory fragment and the C-terminal kinase domain of PAK1 shows that GTPase binding will trigger a series of conformational changes, beginning with disruption of a PAK1 ..
  37. Liu K, Huynh N, Patel O, Shulkes A, BALDWIN G, He H. P21-activated kinase 1 promotes colorectal cancer survival by up-regulation of hypoxia-inducible factor-1?. Cancer Lett. 2013;340:22-9 pubmed publisher
    P21 activated kinase 1 (PAK1) enhances colorectal cancer (CRC) progression by stimulating Wnt/?-catenin and Ras oncogene, which promote CRC survival via stimulation of hypoxia-inducible factor 1? (HIF-1?)...
  38. Rettig M, Trinidad K, Pezeshkpour G, Frost P, Sharma S, Moatamed F, et al. PAK1 kinase promotes cell motility and invasiveness through CRK-II serine phosphorylation in non-small cell lung cancer cells. PLoS ONE. 2012;7:e42012 pubmed publisher
    ..We also provide evidence that PAK1 mediates CRK-II serine 41 phosphorylation...
  39. Parrini M, Lei M, Harrison S, Mayer B. Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell. 2002;9:73-83 pubmed
    b>Pak1, a serine/threonine kinase that regulates the actin cytoskeleton, is an effector of the Rho family GTPases Cdc42 and Rac1. The crystal structure of Pak1 revealed an autoinhibited dimer that must dissociate upon GTPase binding...
  40. Goc A, Al Azayzih A, Abdalla M, Al Husein B, Kavuri S, Lee J, et al. P21 activated kinase-1 (Pak1) promotes prostate tumor growth and microinvasion via inhibition of transforming growth factor ? expression and enhanced matrix metalloproteinase 9 secretion. J Biol Chem. 2013;288:3025-35 pubmed publisher
    ..Among the six isoforms, Pak1 is the most ubiquitous and the best characterized member...
  41. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem. 2000;275:3577-82 pubmed
    ..Together with the recent finding that PAK1, a downstream effector of Rac, also activates LIMK1 by phosphorylation at Thr-508, these results suggest that ..
  42. Yang Z, Rayala S, Nguyen D, Vadlamudi R, Chen S, Kumar R. Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions. Cancer Res. 2005;65:3179-84 pubmed
    ..Since the invasiveness of breast cancer cells is also influenced by p21-activated kinase 1 (Pak1) signaling, we investigated Pak1's potential mechanistic role in the regulation of Snail functions...
  43. Homann S, Tibroni N, Baumann I, Sertel S, Keppler O, Fackler O. Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo. Retrovirology. 2009;6:6 pubmed publisher
    ..This ability might contribute to Nef's pathogenic potential in vivo. ..
  44. Cheng C, Kong X, Wang H, Gan H, Hao Y, Zou W, et al. Trihydrophobin 1 Interacts with PAK1 and Regulates ERK/MAPK Activation and Cell Migration. J Biol Chem. 2009;284:8786-96 pubmed publisher
    ..that trihydrophobin 1 (TH1), originally identified as a negative regulator of A-RAF kinase, also interacted with PAK1 in cultured cells...
  45. Sanders L, Matsumura F, Bokoch G, De Lanerolle P. Inhibition of myosin light chain kinase by p21-activated kinase. Science. 1999;283:2083-5 pubmed
    ..p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity...
  46. Li L, Luo Q, Zheng M, Pan C, Wu G, Lu Y, et al. P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis. Oncol Rep. 2012;27:1435-42 pubmed publisher
    P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis...
  47. Morreale A, Venkatesan M, Mott H, Owen D, Nietlispach D, Lowe P, et al. Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol. 2000;7:384-8 pubmed
    ..The structure, together with mutagenesis data, suggests reasons for the specificity of these interactions and provides insight into the mechanism of PAK activation. ..
  48. Greenway A, Holloway G, McPhee D, Ellis P, Cornall A, Lidman M. HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication. J Biosci. 2003;28:323-35 pubmed
  49. Frost J, Khokhlatchev A, Stippec S, White M, Cobb M. Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation. J Biol Chem. 1998;273:28191-8 pubmed
    ..Different forms of activated PAK1 have been reported to either promote membrane ruffling and focal adhesion assembly or cause focal adhesion ..
  50. Lei M, Robinson M, Harrison S. The active conformation of the PAK1 kinase domain. Structure. 2005;13:769-78 pubmed
    ..A structure of PAK1 in an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces ..
  51. Polzien L, Baljuls A, Rennefahrt U, Fischer A, Schmitz W, Zahedi R, et al. Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation. J Biol Chem. 2009;284:28004-20 pubmed publisher
    ..This pore-forming capacity was dependent on phosphorylation status and interaction with 14-3-3 proteins. Collectively, our findings provide new insights into the regulation of BAD function by phosphorylation. ..
  52. Mott H, Nietlispach D, Evetts K, Owen D. Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK). Biochemistry. 2005;44:10977-83 pubmed
    ..When PAK is activated, Ser-199 in the PIX-binding site is phosphorylated. This phosphorylation is sufficient to reduce the affinity for PIX 6-fold. ..
  53. Sawai E, Khan I, Montbriand P, Peterlin B, Cheng Mayer C, Luciw P. Activation of PAK by HIV and SIV Nef: importance for AIDS in rhesus macaques. Curr Biol. 1996;6:1519-27 pubmed
    ..These findings reveal that there is a strong selective pressure in vivo for the interaction between Nef and the PAK-related kinase. ..
  54. Li F, Adam L, Vadlamudi R, Zhou H, Sen S, Chernoff J, et al. p21-activated kinase 1 interacts with and phosphorylates histone H3 in breast cancer cells. EMBO Rep. 2002;3:767-73 pubmed
    Stimulation of p21-activated kinase-1 (Pak1) signaling promotes motility, invasiveness, anchorage-independent growth and abnormal mitotic assembly in human breast cancer cells...
  55. Weisz Hubsman M, Volinsky N, Manser E, Yablonski D, Aronheim A. Autophosphorylation-dependent degradation of Pak1, triggered by the Rho-family GTPase, Chp. Biochem J. 2007;404:487-97 pubmed
    The Paks (p21-activated kinases) Pak1, Pak2 and Pak3 are among the most studied effectors of the Rho-family GTPases, Rac, Cdc42 (cell division cycle 42) and Chp (Cdc42 homologous protein)...
  56. Dummler B, Ohshiro K, Kumar R, Field J. Pak protein kinases and their role in cancer. Cancer Metastasis Rev. 2009;28:51-63 pubmed publisher
    ..Pak-targeted therapeutics may efficiently inhibit certain types of tumors and efforts to identify selective Pak-inhibitors are underway. ..
  57. Holm C, Rayala S, Jirstrom K, Stal O, Kumar R, Landberg G. Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients. J Natl Cancer Inst. 2006;98:671-80 pubmed
    p21-activated kinase 1 (Pak1) phosphorylates many proteins in both normal and transformed cells...
  58. Chong C, Tan L, Lim L, Manser E. The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity. J Biol Chem. 2001;276:17347-53 pubmed
    ..Thus two autophosphorylation sites direct activation while three others control association with focal complexes via PIX and Nck. ..
  59. Qing H, Gong W, Che Y, Wang X, Peng L, Liang Y, et al. PAK1-dependent MAPK pathway activation is required for colorectal cancer cell proliferation. Tumour Biol. 2012;33:985-94 pubmed publisher
    P21-activated protein kinase1 (PAK1), a main downstream effector of small Rho GTPases, Rac1, and Cdc42, plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis...
  60. Manser E, Leung T, Salihuddin H, Zhao Z, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 1994;367:40-6 pubmed
    ..This bimolecular interaction provides a model for studying p21 regulation of mammalian phosphorylation signalling pathways. ..
  61. Miki H, Yamaguchi H, Suetsugu S, Takenawa T. IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature. 2000;408:732-5 pubmed
    ..From studies of ectopic expression, we found that IRSp53 is essential for Rac to induce membrane ruffling, probably because it recruits WAVE, which stimulates actin polymerization mediated by the Arp2/3 complex. ..
  62. Wang S, Shin I, Wu F, Friedman D, Arteaga C. HER2/Neu (ErbB2) signaling to Rac1-Pak1 is temporally and spatially modulated by transforming growth factor beta. Cancer Res. 2006;66:9591-600 pubmed
    ..kinase (PI3K), recruits actin and actinin to HER2, which then colocalizes with Vav2, activated Rac1, and Pak1 at cell protrusions...
  63. Jin S, Zhuo Y, Guo W, Field J. p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem. 2005;280:24698-705 pubmed
    ..Here we elucidate the molecular mechanism through which Pak1 signals to BAD through a Raf-1-activated pathway...
  64. Lozano E, Frasa M, Smolarczyk K, Knaus U, Braga V. PAK is required for the disruption of E-cadherin adhesion by the small GTPase Rac. J Cell Sci. 2008;121:933-8 pubmed publisher
    ..Instead, activation of the Rac target PAK1 is necessary for destabilization of cell-cell contacts...
  65. King C, Gardiner E, Zenke F, Bohl B, Newton A, Hemmings B, et al. p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). J Biol Chem. 2000;275:41201-9 pubmed
    ..we show that phosphorylated 3-phosphoinositide-dependent kinase 1 (PDK1) phosphorylates p21-activated kinase 1 (PAK1) in the presence of sphingosine...
  66. Turner C, Brown M, Perrotta J, Riedy M, Nikolopoulos S, McDonald A, et al. Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling. J Cell Biol. 1999;145:851-63 pubmed
    ..These data implicate paxillin as a mediator of p21 GTPase-regulated actin cytoskeletal reorganization through the recruitment to nascent focal adhesion structures of an active PAK/PIX complex potentially via interactions with p95PKL. ..
  67. Zegers M, Forget M, Chernoff J, Mostov K, ter Beest M, Hansen S. Pak1 and PIX regulate contact inhibition during epithelial wound healing. EMBO J. 2003;22:4155-65 pubmed
    ..we show that epithelial cells expressing constitutively active or kinase-dead mutants of the Rac/Cdc42 effector Pak1 fail to undergo growth arrest upon wound closure...
  68. Bekri S, Adelaide J, Merscher S, Grosgeorge J, Caroli Bosc F, Perucca Lostanlen D, et al. Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma. Cytogenet Cell Genet. 1997;79:125-31 pubmed
    ..Four new genes were placed on the regional map, namely CBP2, CLNS1A, UVRAG, and PAK1. We have narrowed the core of the 11q13-->q14 amplicon to a 350-kb area encompassing D11S533, mostly on its ..
  69. Vadlamudi R, Li F, Barnes C, Bagheri Yarmand R, Kumar R. p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate. EMBO Rep. 2004;5:154-60 pubmed
    ..Here we show that p41-Arc interacts with p21-activated kinase 1 (Pak1) both in vitro and in vivo...
  70. Schraml P, Schwerdtfeger G, Burkhalter F, Raggi A, Schmidt D, Ruffalo T, et al. Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol. 2003;163:985-92 pubmed
    ..DNA copy number gains were most frequently observed for PIK3CA on 3q (66%), PAK1 on 11q (59%), KRAS2 on 12p (55%), and STK15 on 20q (55%)...
  71. Wang J, Zhou Y, Zou S, Ren T, Zhang Z. Correlations of P21-activated kinase 1 expression to clinicopathological features of gastric carcinoma and patients' prognosis. Chin J Cancer. 2010;29:649-54 pubmed
    Recent studies proved that P21-activated kinase 1 (PAK1) is highly expressed in many kinds of tumor and plays an important role in genesis, development, and metastasis of tumor...
  72. Zang M, Hayne C, Luo Z. Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. J Biol Chem. 2002;277:4395-405 pubmed
    ..Previous studies have shown that Pak1/2 is implicated in both Ras-dependent and -independent activation of Raf-1 by phosphorylating Raf Ser(338)...
  73. Zhu G, Wang Y, Huang B, Liang J, Ding Y, Xu A, et al. A Rac1/PAK1 cascade controls ?-catenin activation in colon cancer cells. Oncogene. 2012;31:1001-12 pubmed publisher
    P21-activated kinase 1 (PAK1) is associated with colon cancer progression and metastasis, whereas the molecular mechanism remains elusive...
  74. Shrestha Y, Schafer E, Boehm J, Thomas S, He F, Du J, et al. PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling. Oncogene. 2012;31:3397-408 pubmed publisher
    ..We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies...
  75. Woolfolk E, Eguchi S, Ohtsu H, Nakashima H, Ueno H, Gerthoffer W, et al. Angiotensin II-induced activation of p21-activated kinase 1 requires Ca2+ and protein kinase C{delta} in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2005;289:C1286-94 pubmed
    ..However, the detailed signaling mechanism by which ANG II induces PAK1 activation in VSMCs remains unclear...
  76. Li L, Zheng M, Luo Q, Ye Q, Feng B, Lu A, et al. P21-activated protein kinase 1 induces colorectal cancer metastasis involving ERK activation and phosphorylation of FAK at Ser-910. Int J Oncol. 2010;37:951-62 pubmed
    b>Pak1 has been reported to be overexpressed in colorectal cancer, but the role of Pak1 in colorectal cancer remains unclear. In this study, Pak1 expression and activity were associated with aggressive behavior of colorectal cancer...
  77. Brown L, Kalloger S, Miller M, Shih I, McKinney S, Santos J, et al. Amplification of 11q13 in ovarian carcinoma. Genes Chromosomes Cancer. 2008;47:481-9 pubmed publisher
    ..this region led to the identification of multiple amplicons containing several potential oncogenes including EMSY, PAK1, RSF1, and GAB2...
  78. Chen L, Liu H, Liu J, Zhu Y, Xu L, He H, et al. Klotho endows hepatoma cells with resistance to anoikis via VEGFR2/PAK1 activation in hepatocellular carcinoma. PLoS ONE. 2013;8:e58413 pubmed publisher
    ..Klotho overexpression elevated p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase activity inhibition with kinase dead mutant PAK1 K299R ..
  79. Edwards D, Sanders L, Bokoch G, Gill G. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol. 1999;1:253-9 pubmed
    ..Here we show that p21-activated kinase (Pak1) phosphorylates LIM-kinase at threonine residue 508 within LIM-kinase's activation loop, and increases LIM-kinase-..
  80. Manser E, Loo T, Koh C, Zhao Z, Chen X, Tan L, et al. PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol Cell. 1998;1:183-92 pubmed
    ..PIX can induce membrane ruffling, with an associated activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1 signaling, involving the PIX/PAK complex. ..
  81. 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...
  82. King A, Sun H, Diaz B, Barnard D, Miao W, Bagrodia S, et al. The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338. Nature. 1998;396:180-3 pubmed
    ..As guanine-nucleotide-exchange activity on Rac can be stimulated by a Ras-dependent phosphatidylinositol-3-OH kinase, a mechanism could exist through which one Ras effector pathway can be influenced by another. ..
  83. Strochlic T, Viaud J, Rennefahrt U, Anastassiadis T, Peterson J. Phosphoinositides are essential coactivators for p21-activated kinase 1. Mol Cell. 2010;40:493-500 pubmed publisher
    Phospholipid-enriched membranes such as the plasma membrane can serve as direct regulators of kinase signaling. Pak1 is involved in growth factor signaling at the plasma membrane, and its dysregulation is implicated in cancer...
  84. Du J, Sun C, Hu Z, Yang Y, Zhu Y, Zheng D, et al. Lysophosphatidic acid induces MDA-MB-231 breast cancer cells migration through activation of PI3K/PAK1/ERK signaling. PLoS ONE. 2010;5:e15940 pubmed publisher
    ..In addition, LPA induced PAK1 activation while ERK activation and cell migration were inhibited by ectopic expression of an inactive mutant form ..
  85. Xiao G, Beeser A, Chernoff J, Testa J. p21-activated kinase links Rac/Cdc42 signaling to merlin. J Biol Chem. 2002;277:883-6 pubmed
    ..These biochemical investigations provide insights into the regulation of merlin function and establish a framework for elucidating tumorigenic mechanisms involved in neoplasms associated with merlin inactivation. ..
  86. Chow H, Jubb A, Koch J, Jaffer Z, Stepanova D, Campbell D, et al. p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model. Cancer Res. 2012;72:5966-75 pubmed publisher
    ..As p21-activated kinase 1 (Pak1) has been shown to regulate both these signaling pathways and is itself upregulated in many human cancers, we ..
  87. Ishida H, Li K, Yi M, Lemon S. p21-activated kinase 1 is activated through the mammalian target of rapamycin/p70 S6 kinase pathway and regulates the replication of hepatitis C virus in human hepatoma cells. J Biol Chem. 2007;282:11836-48 pubmed
    ..p21-activated kinase 1 (PAK1) is a serine/threonine kinase that has been suggested to participate in antiviral signaling...
  88. Reddy S, Ohshiro K, Rayala S, Kumar R. MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res. 2008;68:8195-200 pubmed publisher
    ..Here we show that microRNA-7 (miR-7) inhibits p21-activated kinase 1 (Pak1) expression, a widely up-regulated signaling kinase in multiple human cancers, by targeting the 3'-untranslated ..
  89. Dammann K, Khare V, Gasche C. Tracing PAKs from GI inflammation to cancer. Gut. 2014;63:1173-84 pubmed publisher
    ..Intestinal PAK1 expression increases with inflammation and malignant transformation, although the biological relevance of PAKs in ..
  90. Bostner J, Skoog L, Fornander T, Nordenskjold B, Stal O. Estrogen receptor-alpha phosphorylation at serine 305, nuclear p21-activated kinase 1 expression, and response to tamoxifen in postmenopausal breast cancer. Clin Cancer Res. 2010;16:1624-33 pubmed publisher
    In vitro, p21-activated kinase 1 (Pak1) phosphorylates the serine 305 residue of the estrogen receptor alpha (ERalpha) and influences the response of breast cancer cells to tamoxifen...
  91. Pavey S, Zuidervaart W, van Nieuwpoort F, Packer L, Jager M, Gruis N, et al. Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma. Melanoma Res. 2006;16:285-96 pubmed
    ..Of particular interest, expression of two members of the p21-activated kinase (PAK) family, PAK1 and PAK7, was elevated in the more invasive cultures...