Pak2

Summary

Gene Symbol: Pak2
Description: p21 (RAC1) activated kinase 2
Alias: 5330420P17Rik, A130002K10Rik, AI836325, D16Ertd269e, PAK-2, mKIAA4182, serine/threonine-protein kinase PAK 2, gamma-PAK, p21 protein (Cdc42/Rac)-activated kinase 2, p21-activated kinase 2
Species: mouse
Products:     Pak2

Top Publications

  1. Marler K, Kozma R, Ahmed S, Dong J, Hall C, Lim L. Outgrowth of neurites from NIE-115 neuroblastoma cells is prevented on repulsive substrates through the action of PAK. Mol Cell Biol. 2005;25:5226-41 pubmed
    ..Thus, while neurite outgrowth can be promoted by RhoA inhibition, overcoming the accompanying repulsive guidance response will require modulation of PAK activity. These results have therapeutic implications for CNS repair processes. ..
  2. Kreis P, Rousseau V, Thévenot E, Combeau G, Barnier J. The four mammalian splice variants encoded by the p21-activated kinase 3 gene have different biological properties. J Neurochem. 2008;106:1184-97 pubmed publisher
    The p21-activated kinases (PAK1), PAK2, and PAK3 are members of the PAK group I and share high sequence identity and common biochemical properties...
  3. Kosoff R, Chow H, Radu M, Chernoff J. Pak2 kinase restrains mast cell Fc?RI receptor signaling through modulation of Rho protein guanine nucleotide exchange factor (GEF) activity. J Biol Chem. 2013;288:974-83 pubmed publisher
    ..Another isoform in this kinase family, Pak2, is expressed at very high levels in mast cells, but its function is unknown...
  4. Vincent P, Priceputu E, Kay D, Saksela K, Jolicoeur P, Hanna Z. Activation of p21-activated kinase 2 and its association with Nef are conserved in murine cells but are not sufficient to induce an AIDS-like disease in CD4C/HIV transgenic mice. J Biol Chem. 2006;281:6940-54 pubmed
    ..simian immunodeficiency virus (SIV) Nef is the interaction with and activation of the human p21-activated kinase 2 (PAK2)...
  5. Piccand J, Meunier A, Merle C, Jia Z, Barnier J, Gradwohl G. Pak3 promotes cell cycle exit and differentiation of ?-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice. Diabetes. 2014;63:203-15 pubmed publisher
    ..In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD. ..
  6. Radu M, Lyle K, Hoeflich K, Villamar Cruz O, Koeppen H, Chernoff J. p21-Activated Kinase 2 Regulates Endothelial Development and Function through the Bmk1/Erk5 Pathway. Mol Cell Biol. 2015;35:3990-4005 pubmed publisher
    ..there is no consensus on the endothelial function of individual Pak isoforms, in particular p21-activated kinase 2 (Pak2), the main Pak isoform expressed in endothelial cells...
  7. Rosario M, Schuster S, Jüttner R, Parthasarathy S, Tarabykin V, Birchmeier W. Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin. Genes Dev. 2012;26:1743-57 pubmed publisher
    ..Our findings define a novel cell-intrinsic mechanism to regulate dendritic branching and thus neuronal complexity in the cerebral cortex. ..
  8. Chen Y, Stump R, Lovicu F, Shimono A, McAvoy J. Wnt signaling is required for organization of the lens fiber cell cytoskeleton and development of lens three-dimensional architecture. Dev Biol. 2008;324:161-76 pubmed publisher
    ..Components of the Wnt/Planar Cell Polarity (PCP) pathway were downregulated or inhibited. Taken together this supports a role for Wnt/PCP signaling in orchestrating the complex organization and dynamics of the fiber cell cytoskeleton...
  9. Marlin J, Chang Y, Ober M, Handy A, Xu W, Jakobi R. Functional PAK-2 knockout and replacement with a caspase cleavage-deficient mutant in mice reveals differential requirements of full-length PAK-2 and caspase-activated PAK-2p34. Mamm Genome. 2011;22:306-17 pubmed publisher

More Information

Publications47

  1. Kosoff R, Aslan J, Kostyak J, Dulaimi E, Chow H, Prudnikova T, et al. Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization. Blood. 2015;125:2995-3005 pubmed publisher
    ..Here, we identify Pak2 as an essential effector of megakaryocyte maturation, polyploidization, and proplatelet formation...
  2. Lee K, Yonehara S. Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST). J Biol Chem. 2002;277:12351-8 pubmed
  3. Li X, Minden A. Targeted disruption of the gene for the PAK5 kinase in mice. Mol Cell Biol. 2003;23:7134-42 pubmed
    ..The nervous system appears normal in the absence of PAK5, as do other tissues in which PAK5 is normally expressed. Our results suggest functional redundancy between PAK5 and other Rho GTPase targets. ..
  4. Dorrance A, De Vita S, Radu M, Reddy P, McGuinness M, Harris C, et al. The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment. Blood. 2013;121:2474-82 pubmed publisher
    ..Using conditional knock-out mice, we demonstrate that among group A Paks, Pak2(-/-) HSPC show reduced homing to the bone marrow and altered cell shape similar to PID-LSK cells in vitro and are ..
  5. Kurakin A, Wu S, Bredesen D. Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. J Biol Chem. 2003;278:34102-9 pubmed
    ..Synaptojanin 1, PAK2, ZO-2, and TAFII70, which contain CIN85 SH3 recognition consensus sites, were selectively precipitated from mouse ..
  6. Wilkes M, Leof E. Transforming growth factor beta activation of c-Abl is independent of receptor internalization and regulated by phosphatidylinositol 3-kinase and PAK2 in mesenchymal cultures. J Biol Chem. 2006;281:27846-54 pubmed
    ..by TGF-beta is independent of Smad2 or Smad3, it is prevented by inhibitors of phosphatidylinositol 3-kinase or PAK2. Thus, c-Abl represents a target downstream of phosphatidylinositol 3-kinase-activated PAK2, which differentiates ..
  7. Demyanenko G, Halberstadt A, Rao R, Maness P. CHL1 cooperates with PAK1-3 to regulate morphological differentiation of embryonic cortical neurons. Neuroscience. 2010;165:107-15 pubmed publisher
    ..These findings suggest that CHL1 and PAK1-3 kinase cooperate, most likely in independent pathways, in regulating morphological development of the leading process/apical dendrite of embryonic cortical neurons. ..
  8. Gadepalli R, Kotla S, Heckle M, Verma S, Singh N, Rao G. Novel role for p21-activated kinase 2 in thrombin-induced monocyte migration. J Biol Chem. 2013;288:30815-31 pubmed publisher
    ..Thrombin induced tyrosine phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA-dependent Pak2 activation. Downstream to Pyk2, Gab1 formed a complex with p115 RhoGEF involving their pleckstrin homology domains...
  9. Burbelo P, Kozak C, Finegold A, Hall A, Pirone D. Cloning, central nervous system expression and chromosomal mapping of the mouse PAK-1 and PAK-3 genes. Gene. 1999;232:209-15 pubmed
    ..The high level of PAK-1 and PAK-3 kinase expression in the mouse brain and spinal cord suggests a potentially important role for these kinases in the control of the cellular architecture and/or signaling in the central nervous system. ..
  10. Dolan B, Duron S, Campbell D, Vollrath B, Shankaranarayana Rao B, Ko H, et al. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A. 2013;110:5671-6 pubmed publisher
    ..Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult Fmr1 KO mice, demonstrating the potential for rapid, postdiagnostic therapy in adults with FXS. ..
  11. Sipe C, Liu L, Lee J, Grimsley Myers C, Lu X. Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization. Development. 2013;140:1785-95 pubmed publisher
    ..Together, our results demonstrate that Lis1 mediates the planar polarity of hair cells through regulation of microtubule organization downstream of the tissue polarity pathway. ..
  12. Hsuuw Y, Kuo T, Lee K, Liu Y, Huang Y, Lai C, et al. Ginkgolide B induces apoptosis via activation of JNK and p21-activated protein kinase 2 in mouse embryonic stem cells. Ann N Y Acad Sci. 2009;1171:501-8 pubmed publisher
    ..induced apoptotic biochemical changes, including activation of JNK, caspase-3, and p21-activated protein kinase 2 (PAK2), in ESC-B5 mouse embryonic stem cells...
  13. Luo S, Rubinsztein D. Huntingtin promotes cell survival by preventing Pak2 cleavage. J Cell Sci. 2009;122:875-85 pubmed publisher
    ..When cells are exposed to Fas-related signals, the ubiquitously expressed p21-activated kinase 2 (Pak2) can be activated via cleavage by caspases to release a constitutively active C-terminal fragment, which mediates ..
  14. Coll P, Trillo Y, Ametzazurra A, Perez P. Gef1p, a new guanine nucleotide exchange factor for Cdc42p, regulates polarity in Schizosaccharomyces pombe. Mol Biol Cell. 2003;14:313-23 pubmed
    ..Genetic evidence revealed a link between Gef1p and the signaling pathway of Shk1/Orb2p and Orb6p. In contrast, no genetic interaction between Gef1p and Shk2p-Mkh1p pathway was observed. ..
  15. Machuy N, Campa F, Thieck O, Rudel T. c-Abl-binding protein interacts with p21-activated kinase 2 (PAK-2) to regulate PDGF-induced membrane ruffles. J Mol Biol. 2007;370:620-32 pubmed
    ..Our findings define a new class of PAK-interacting proteins, which play an important role in actin cytoskeletal reorganization. ..
  16. Grimsley Myers C, Sipe C, Géléoc G, Lu X. The small GTPase Rac1 regulates auditory hair cell morphogenesis. J Neurosci. 2009;29:15859-69 pubmed publisher
    ..Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle...
  17. Misra U, Sharma T, Pizzo S. Ligation of cell surface-associated glucose-regulated protein 78 by receptor-recognized forms of alpha 2-macroglobulin: activation of p21-activated protein kinase-2-dependent signaling in murine peritoneal macrophages. J Immunol. 2005;175:2525-33 pubmed
    ..Thus, alpha2M* regulates activation of the PAK-2-dependent motility mechanism in these cells. ..
  18. Zhang H, Webb D, Asmussen H, Niu S, Horwitz A. A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and synapse formation through MLC. J Neurosci. 2005;25:3379-88 pubmed
  19. Orton K, Ling J, Waskiewicz A, Cooper J, Merrick W, Korneeva N, et al. Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. J Biol Chem. 2004;279:38649-57 pubmed
    The mitogen-activated protein kinase-interacting kinase 1 (Mnk1) is phosphorylated by caspase-cleaved protein kinase Pak2/gamma-PAK but not by Cdc42-activated Pak2...
  20. Hayashi K, Ohshima T, Mikoshiba K. Pak1 is involved in dendrite initiation as a downstream effector of Rac1 in cortical neurons. Mol Cell Neurosci. 2002;20:579-94 pubmed
    ..These results suggest that Pak1 regulates dendrite initiation as a downstream effector of Rac1. ..
  21. Phee H, Au Yeung B, Pryshchep O, O Hagan K, Fairbairn S, Radu M, et al. Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation. elife. 2014;3:e02270 pubmed publisher
    ..The P21-activated kinase 2 (Pak2) is an effector for the Rho family GTPases Rac and Cdc42 that regulate actin cytoskeletal remodeling, but its role ..
  22. Zeng Y, Broxmeyer H, Staser K, Chitteti B, Park S, Hahn S, et al. Pak2 regulates hematopoietic progenitor cell proliferation, survival, and differentiation. Stem Cells. 2015;33:1630-41 pubmed publisher
    p21-Activated kinase 2 (Pak2), a serine/threonine kinase, has been previously shown to be essential for hematopoietic stem cell (HSC) engraftment...
  23. Chintala H, Krupska I, Yan L, LAU L, Grant M, Chaqour B. The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling. Development. 2015;142:2364-74 pubmed publisher
    ..These data highlight novel functions of CCN1 as a naturally optimized molecule, fine-controlling key processes in physiological angiogenesis and safeguarding against aberrant angiogenic responses. ..
  24. Varshney P, Dey C. Resveratrol regulates neuronal glucose uptake and insulin sensitivity via P21-activated kinase 2 (PAK2). Biochem Biophys Res Commun. 2017;485:372-378 pubmed publisher
    We have recently reported P21-activated kinase 2 (PAK2), a serine/threonine kinase as a negative regulator of neuronal glucose uptake and insulin sensitivity...
  25. Chang J, Ni Y, Han L, Sinnett Smith J, Jacamo R, Rey O, et al. Protein kinase D1 (PKD1) phosphorylation on Ser203 by type I p21-activated kinase (PAK) regulates PKD1 localization. J Biol Chem. 2017;292:9523-9539 pubmed publisher
    ..different mechanisms abrogated PKD1 phosphorylation at Ser203, 2) siRNA-mediated knockdown of PAK1 and PAK2 in IEC-18 and Swiss 3T3 cells blunted PKD1 phosphorylation at Ser203, 3) phosphorylation of Ser203
  26. Jiang X, Wassif C, Backlund P, Song L, Holtzclaw L, Li Z, et al. Activation of Rho GTPases in Smith-Lemli-Opitz syndrome: pathophysiological and clinical implications. Hum Mol Genet. 2010;19:1347-57 pubmed publisher
    ..Developmental abnormalities of neuronal process formation may contribute to the neurocognitive deficits found in SLOS and may represent a potential target for therapeutic intervention. ..
  27. Nola S, Sebbagh M, Marchetto S, Osmani N, Nourry C, Audebert S, et al. Scrib regulates PAK activity during the cell migration process. Hum Mol Genet. 2008;17:3552-65 pubmed publisher
    ..These data underscore the role of Scrib in cell migration and show the strong impact of Scrib in the function of PAK and Rac, two key molecules implicated in this process. ..
  28. Kissil J, Johnson K, Eckman M, Jacks T. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J Biol Chem. 2002;277:10394-9 pubmed
    ..We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and ..
  29. O Hagan K, Choi J, Pryshchep O, Chernoff J, Phee H. Pak2 Links TCR Signaling Strength to the Development of Regulatory T Cells and Maintains Peripheral Tolerance. J Immunol. 2015;195:1564-77 pubmed publisher
    ..Our findings show a novel role for the actin cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), in Treg development and homeostasis...
  30. Huang Z, Traugh J, Bishop J. Negative control of the Myc protein by the stress-responsive kinase Pak2. Mol Cell Biol. 2004;24:1582-94 pubmed
    b>Pak2 is a serine/threonine kinase that participates in the cellular response to stress. Among the potential substrates for Pak2 is the protein Myc, encoded by the proto-oncogene MYC...
  31. O Hagan K, Zhao J, Pryshchep O, Wang C, Phee H. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2. J Immunol. 2015;195:5272-84 pubmed publisher
    ..In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development...
  32. Varshney P, Dey C. P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells. Mol Cell Endocrinol. 2016;429:50-61 pubmed publisher
    ..However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance...
  33. Jakobi R, McCarthy C, Koeppel M, Stringer D. Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation. J Biol Chem. 2003;278:38675-85 pubmed
    ..Therefore, nuclear targeting and inhibition of degradation appear to be critical for stimulation of the cell death response by PAK-2p34. ..
  34. Van den Broeke C, Radu M, Deruelle M, Nauwynck H, Hofmann C, Jaffer Z, et al. Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases. Proc Natl Acad Sci U S A. 2009;106:8707-12 pubmed publisher
    ..By using PAK1(-/-) and PAK2(-/-) mouse embryo fibroblasts (MEFs), we show that US3-mediated stress fiber disassembly requires PAK2, whereas US3-..
  35. Weiss Haljiti C, Pasquali C, Ji H, Gillieron C, Chabert C, Curchod M, et al. Involvement of phosphoinositide 3-kinase gamma, Rac, and PAK signaling in chemokine-induced macrophage migration. J Biol Chem. 2004;279:43273-84 pubmed
    ..on activation normal T cell expressed and secreted)/CCL5 activates the small GTPase Rac and its downstream target PAK2 within seconds...
  36. Reddy P, Radu M, Xu K, Wood J, Harris C, Chernoff J, et al. p21-activated kinase 2 regulates HSPC cytoskeleton, migration, and homing via CDC42 activation and interaction with β-Pix. Blood. 2016;127:1967-75 pubmed publisher
    ..C3 botulinum toxin substrate (Rac)/cell division control protein 42 homolog (CDC42) effector p21-activated kinase (Pak2) has been implicated in HSPC homing and engraftment...
  37. Joseph G, Lu M, Radu M, Lee J, Burden S, Chernoff J, et al. Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro. Mol Cell Biol. 2017;37: pubmed publisher
    ..The group I Paks Pak1 and Pak2 are related protein kinases and direct effectors of Cdc42 and Rac1...
  38. Koeppel M, McCarthy C, Moertl E, Jakobi R. Identification and characterization of PS-GAP as a novel regulator of caspase-activated PAK-2. J Biol Chem. 2004;279:53653-64 pubmed
    ..Furthermore, PS-GAP decreases the stimulation of cell death induced by stabilization of PAK-2p34. ..