Pak2

Summary

Gene Symbol: Pak2
Description: p21 (RAC1) activated kinase 2
Alias: PAK65, PAKgamma, serine/threonine-protein kinase PAK 2, PAK-2, S6/H4 kinase, gamma-PAK, p21 (CDKN1A)-activated kinase 2, p21 protein (Cdc42/Rac)-activated kinase 2, p21-activated kinase 2, p58
Species: human
Products:     Pak2

Top Publications

  1. Baur A, Sass G, Laffert B, Willbold D, Cheng Mayer C, Peterlin B. The N-terminus of Nef from HIV-1/SIV associates with a protein complex containing Lck and a serine kinase. Immunity. 1997;6:283-91 pubmed
    ..Deletion of a short amphipathic alpha-helix in the N-terminus, which was found to be conserved in all Nef proteins, inhibited association of the NAKC and significantly reduced virion infectivity. ..
  2. Rauch S, Pulkkinen K, Saksela K, Fackler O. Human immunodeficiency virus type 1 Nef recruits the guanine exchange factor Vav1 via an unexpected interface into plasma membrane microdomains for association with p21-activated kinase 2 activity. J Virol. 2008;82:2918-29 pubmed
    ..virus type 1 (HIV-1) Nef involve its association with a highly active subpopulation of p21-activated kinase 2 (PAK2) within a dynamic signalosome assembled in detergent-insoluble membrane microdomains...
  3. Chew T, Masaracchia R, Goeckeler Z, Wysolmerski R. Phosphorylation of non-muscle myosin II regulatory light chain by p21-activated kinase (gamma-PAK). J Muscle Res Cell Motil. 1998;19:839-54 pubmed
    ..Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization. ..
  4. 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-..
  5. Wu H, Zheng Y, Wang Z. Evaluation of the catalytic mechanism of the p21-activated protein kinase PAK2. Biochemistry. 2003;42:1129-39 pubmed
    ..In the present study, we provide an in-depth kinetic analysis of one of the PAK family members, PAK2, in phosphorylation of a protein substrate, myelin basic protein (MBP), and a synthetic peptide substrate derived ..
  6. 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. ..
  7. Agopian K, Wei B, Garcia J, Gabuzda D. A hydrophobic binding surface on the human immunodeficiency virus type 1 Nef core is critical for association with p21-activated kinase 2. J Virol. 2006;80:3050-61 pubmed
    The interaction of human immunodeficiency virus type 1 (HIV-1) Nef with p21-activated kinase 2 (Pak2) has been proposed to play an important role in T-cell activation and disease progression during viral infection...
  8. Wei B, Arora V, Raney A, Kuo L, Xiao G, O Neill E, et al. Activation of p21-activated kinase 2 by human immunodeficiency virus type 1 Nef induces merlin phosphorylation. J Virol. 2005;79:14976-80 pubmed
    ..virus type 1 (HIV-1) protein Nef activates the autophosphorylation activity of p21-activated kinase 2 (PAK2)...
  9. Haller C, Rauch S, Michel N, Hannemann S, Lehmann M, Keppler O, et al. The HIV-1 pathogenicity factor Nef interferes with maturation of stimulatory T-lymphocyte contacts by modulation of N-Wasp activity. J Biol Chem. 2006;281:19618-30 pubmed
    ..Nef activity critically depended on its Src homology 3 domain binding motif and required efficient association with Pak2 activity...

More Information

Publications72

  1. Stove V, Naessens E, Stove C, Swigut T, Plum J, Verhasselt B. Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development. Blood. 2003;102:2925-32 pubmed
    ..acidic cluster sorting protein-1 (PACS-1), Src homology domain 3 (SH3) domains, and p21-activated kinase 2 (PAK2), were found to be critical for its effect on T-cell development...
  2. Kuo L, Baugh L, Denial S, Watkins R, Liu M, Garcia J, et al. Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix. Retrovirology. 2012;9:47 pubmed publisher
    ..that mutations of either of the prolines or the arginine of PXXPXR are defective for Nef-Hck binding, Nef/activated PAK2 complex formation and enhancement of virion infectivity (EVI)...
  3. Krautkrämer E, Giese S, Gasteier J, Muranyi W, Fackler O. Human immunodeficiency virus type 1 Nef activates p21-activated kinase via recruitment into lipid rafts. J Virol. 2004;78:4085-97 pubmed
    ..Together, these data suggest that Nef induces signal transduction via the recruitment of a signaling machinery including Pak into lipid rafts, thereby mimicking a physiological cellular mechanism to initiate the TCR cascade. ..
  4. Kirchhoff F, Schindler M, Bailer N, Renkema G, Saksela K, Knoop V, et al. Nef proteins from simian immunodeficiency virus-infected chimpanzees interact with p21-activated kinase 2 and modulate cell surface expression of various human receptors. J Virol. 2004;78:6864-74 pubmed
  5. Jung J, Traugh J. Regulation of the interaction of Pak2 with Cdc42 via autophosphorylation of serine 141. J Biol Chem. 2005;280:40025-31 pubmed
    b>Pak2, a member of the p21-activated protein kinase (Pak) family, is activated in response to a variety of stresses and is directly involved in the induction of cytostasis...
  6. O Neill E, Baugh L, Novitsky V, Essex M, Garcia J. Intra- and intersubtype alternative Pak2-activating structural motifs of human immunodeficiency virus type 1 Nef. J Virol. 2006;80:8824-9 pubmed
    ..Here, we present evidence that subtype C Nefs display functional Pak2-activating motifs that differ from those found in subtype B and E Nefs...
  7. Foster J, Garcia J. HIV-1 Nef: at the crossroads. Retrovirology. 2008;5:84 pubmed publisher
    ..Specifically, we consider CD4 downregulation, major histocompatibility complex I downregulation, Pak2 activation, and enhancement of virion infectivity...
  8. Meuwissen P, Stolp B, Iannucci V, Vermeire J, Naessens E, Saksela K, et al. Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function. Retrovirology. 2012;9:34 pubmed publisher
    ..Moreover, Nef's association with the cellular p21-activated kinase 2 (PAK2), the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase ..
  9. Knaus U, Morris S, Dong H, Chernoff J, Bokoch G. Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors. Science. 1995;269:221-3 pubmed
    ..The action of PAKs during phagocyte activation by G protein-coupled pathways may contribute to regulation of NADPH oxidase activity. ..
  10. Agopian K, Wei B, Garcia J, Gabuzda D. CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable. Virology. 2007;358:119-35 pubmed
    ..b>Pak2 association was highly variable in Nefs from both patients...
  11. Baugh L, Garcia J, Foster J. Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain. J Virol. 2008;82:9657-67 pubmed publisher
    ..Our results are consistent with an alternative model in which (62)EEEE(65) plays a stabilizing role in the formation of a ternary complex between Nef, the MHC-I cytoplasmic domain, and AP-1. ..
  12. Li X, Wen W, Liu K, Zhu F, Malakhova M, Peng C, et al. Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines. J Biol Chem. 2011;286:22291-9 pubmed publisher
    ..However, the role of PAK2 in resistance to chemotherapy is unclear...
  13. 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
  14. Renkema G, Manninen A, Saksela K. Human immunodeficiency virus type 1 Nef selectively associates with a catalytically active subpopulation of p21-activated kinase 2 (PAK2) independently of PAK2 binding to Nck or beta-PIX. J Virol. 2001;75:2154-60 pubmed
    We have recently identified the Nef-associated serine-threonine kinase (NAK) as the p21-activated kinase 2 (PAK2)...
  15. Vermeire J, Vanbillemont G, Witkowski W, Verhasselt B. The Nef-infectivity enigma: mechanisms of enhanced lentiviral infection. Curr HIV Res. 2011;9:474-89 pubmed
    ..Hereby we aim to contribute to a better understanding of this highly conserved and therapeutically attractive Nef function. ..
  16. Chu P, Wu J, Liao X, Pardo J, Zhao H, Li C, et al. A novel role for p21-activated protein kinase 2 in T cell activation. J Immunol. 2004;172:7324-34 pubmed
    ..In addition to known regulators, two truncated forms of p21-activated kinase 2 (PAK2), PAK2DeltaL(1-224) and PAK2DeltaS(1-113), both lacking the kinase domain, were isolated in the T cell screen...
  17. 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
    ..Purification of p65 and subsequent peptide sequencing revealed identity to rat brain PAK65 and to yeast STE20 kinase domains...
  18. Bright M, Garner A, Ridley A. PAK1 and PAK2 have different roles in HGF-induced morphological responses. Cell Signal. 2009;21:1738-47 pubmed publisher
    ..Several Rho GTPases are required for HGF-induced scattering. PAK1 and PAK2 are members of the p21-activated kinase (PAK) family of serine/threonine kinases, and are activated by the Rho ..
  19. Renkema G, Manninen A, Mann D, Harris M, Saksela K. Identification of the Nef-associated kinase as p21-activated kinase 2. Curr Biol. 1999;9:1407-10 pubmed
    ..By using these reagents in experiments involving partial proteolytic mapping, and exploiting the unique ability of PAK2 to serve as a caspase substrate, we have positively identified NAK as PAK2...
  20. Olivieri K, Mukerji J, Gabuzda D. Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2. Retrovirology. 2011;8:64 pubmed publisher
    ..Nef interacts with a multiprotein signaling complex that includes Src family kinases, Vav1, CDC42, and activated PAK2 (p21-activated kinase 2)...
  21. Stolp B, Abraham L, Rudolph J, Fackler O. Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling. J Virol. 2010;84:3935-48 pubmed publisher
    ..the potent interference of Nef with T-lymphocyte chemotaxis via its association with the cellular kinase PAK2. Mechanistic analysis revealed that this interaction results in deregulation of the actin-severing factor cofilin ..
  22. Walter B, Huang Z, Jakobi R, Tuazon P, Alnemri E, Litwack G, et al. Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). Effects of autophosphorylation on activity. J Biol Chem. 1998;273:28733-9 pubmed
    p21-activated protein kinase gamma-PAK (Pak2, PAK I) is cleaved by CPP32 (caspase 3) during apoptosis and plays a key role in regulation of cell death...
  23. 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. ..
  24. Li T, Zhang J, Zhu F, Wen W, Zykova T, Li X, et al. P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation. Carcinogenesis. 2011;32:659-66 pubmed publisher
    ..Our data showed that PAK2 binds and phosphorylates c-Jun at five threonine sites (Thr2, Thr8, Thr89, Thr93 and Thr286) in vitro and ex vivo...
  25. 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...
  26. Abraham L, Fackler O. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun Signal. 2012;10:39 pubmed publisher
    ..We also discuss the implications of these alterations in the context of HIV-1 infection and in light of current concepts of TCR signal transduction. ..
  27. Giese S, Woerz I, Homann S, Tibroni N, Geyer M, Fackler O. Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) Nef. Virology. 2006;355:175-91 pubmed
    ..was largely unaffected by mutations of all N-terminal basic residues, while the association of Nef with Pak2 kinase activity and its ability to augment virion infectivity correlated with its lysine-mediated raft ..
  28. Roig J, Traugh J. Cytostatic p21 G protein-activated protein kinase gamma-PAK. Vitam Horm. 2001;62:167-98 pubmed
    The p21-activated protein kinase gamma-PAK, also known as PAK2, has very different properties from the other two highly conserved isoforms of the PAK family, alpha-PAK (PAK1) and beta-PAK (PAK3)...
  29. Swingler S, Gallay P, Camaur D, Song J, Abo A, Trono D. The Nef protein of human immunodeficiency virus type 1 enhances serine phosphorylation of the viral matrix. J Virol. 1997;71:4372-7 pubmed
    ..Recombinant p21-activated kinase hPAK65, a recently proposed relative of the Nef-associated kinase, achieved a comparable result. Taken together, these data suggest that MA is a target of the Nef-associated serine kinase. ..
  30. 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. ..
  31. Foster J, Denial S, Temple B, Garcia J. Mechanisms of HIV-1 Nef function and intracellular signaling. J Neuroimmune Pharmacol. 2011;6:230-46 pubmed publisher
    ..The poorly understood Nef functions of p21 activated protein kinase (PAK2) activation, enhancement of virion infectivity, and inhibition of immunoglobulin class switching are also likely to ..
  32. 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
    ..Thus, unlike other members of the PAK family, PAK4 provides a novel link between Cdc42Hs and the actin cytoskeleton. The cellular locations of PAK4 and Cdc42Hs suggest a role for the Golgi in cell morphogenesis. ..
  33. Haller C, Rauch S, Fackler O. HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodeling. PLoS ONE. 2007;2:e1212 pubmed
    ..IS recruitment of Lck were governed by identical Nef determinants and correlated well with Nef's association with Pak2 kinase activity...
  34. Arora V, Molina R, Foster J, Blakemore J, Chernoff J, Fredericksen B, et al. Lentivirus Nef specifically activates Pak2. J Virol. 2000;74:11081-7 pubmed
    ..The exact identity of Nak remains controversial, with two recent studies indicating that Nak may be either Pak1 or Pak2. In this study, we investigated the hypothesis that such discrepancies arise from the use of different Nef alleles ..
  35. Kärkkäinen S, Hiipakka M, Wang J, Kleino I, Vähä Jaakkola M, Renkema G, et al. Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome. EMBO Rep. 2006;7:186-91 pubmed
    ..showing potentially important new SH3-directed interactions, these studies also led to the discovery of novel signalling proteins, such as the PAK2-binding adaptor protein POSH2 and the ADAM15-binding sorting nexin family member SNX30.
  36. Coniglio S, Zavarella S, Symons M. Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms. Mol Cell Biol. 2008;28:4162-72 pubmed publisher
    ..Pak kinases are thought to play critical roles in cell migration and invasion. Here, we analyze the roles of Pak1 and Pak2 in breast carcinoma cell invasion using the transient transfection of small interfering RNA...
  37. Schindler M, Rajan D, Specht A, Ritter C, Pulkkinen K, Saksela K, et al. Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue. J Virol. 2007;81:13005-14 pubmed
    Interaction of the human immunodeficiency virus type 1 (HIV-1) Nef protein with p21-activated kinase 2 (PAK2) has been proposed to play a role in T-cell activation, viral replication, apoptosis, and progression to AIDS...
  38. Vilas G, Corvi M, Plummer G, Seime A, Lambkin G, Berthiaume L. Posttranslational myristoylation of caspase-activated p21-activated protein kinase 2 (PAK2) potentiates late apoptotic events. Proc Natl Acad Sci U S A. 2006;103:6542-7 pubmed
    ..We demonstrate that the caspase-cleaved PAK2 C-terminal kinase fragment (C-t-PAK2) is posttranslationally myristoylated, although myristoylation is typically a ..
  39. Kouwenhoven A, Minassian V, Marsh J. HIV-1 Nef mediates Pak phosphorylation of Mek1 serine298 and elicits an active phospho-state of Pak2. Curr HIV Res. 2013;11:198-209 pubmed
    ..The protein has also been found to associate with and promote autophosphorylation of a serine kinase, Pak2, but the Nef-associated kinase level is very low and difficult to study...
  40. Stolp B, Fackler O. How HIV takes advantage of the cytoskeleton in entry and replication. Viruses. 2011;3:293-311 pubmed publisher
  41. Foster J, Garcia J. Role of Nef in HIV-1 replication and pathogenesis. Adv Pharmacol. 2007;55:389-409 pubmed
  42. Stolp B, Reichman Fried M, Abraham L, Pan X, Giese S, Hannemann S, et al. HIV-1 Nef interferes with host cell motility by deregulation of Cofilin. Cell Host Microbe. 2009;6:174-86 pubmed publisher
    ..Nef-dependent cofilin deregulation requires association of Nef with the cellular kinase Pak2. Disruption of Nef-Pak2 association restores the cofilin phosphorylation levels and actin remodeling that ..
  43. Fuchsova B, Alvarez Juliá A, Rizavi H, Frasch A, Pandey G. Expression of p21-activated kinases 1 and 3 is altered in the brain of subjects with depression. Neuroscience. 2016;333:331-44 pubmed publisher
    ..Using quantitative polymerase chain reaction (qPCR), mRNA levels and coexpression of the group I PAKs: PAK1, PAK2, and PAK3 as well as of their activators: RAC1, CDC42 and ARHGEF7 were examined in postmortem samples from the PFC (..
  44. Lyons J, Brubaker D, Ghazi P, Baldwin K, Edwards A, Boukhali M, et al. Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis. Sci Signal. 2018;11: pubmed publisher
    ..Chemical inhibition of Pak1 and Pak2 with FRAX597 suppressed active colitis in mice...
  45. Hsu Y, Traugh J. Reciprocally coupled residues crucial for protein kinase Pak2 activity calculated by statistical coupling analysis. PLoS ONE. 2010;5:e9455 pubmed publisher
    Regulation of Pak2 activity involves at least two mechanisms: (i) phosphorylation of the conserved Thr(402) in the activation loop and (ii) interaction of the autoinhibitory domain (AID) with the catalytic domain...
  46. Benner G, Dennis P, Masaracchia R. Activation of an S6/H4 kinase (PAK 65) from human placenta by intramolecular and intermolecular autophosphorylation. J Biol Chem. 1995;270:21121-8 pubmed
    ..These sequences identify S6H4 kinase as the rac-activated PAK65 (Martin, G. A., Bollag, G., McCormick, F. and Abo, A. (1995) EMBO J. 14, 1971-1978)...
  47. Bokoch G. Caspase-mediated activation of PAK2 during apoptosis: proteolytic kinase activation as a general mechanism of apoptotic signal transduction?. Cell Death Differ. 1998;5:637-45 pubmed
    p21-activated kinase 2 (PAK2) is proteolytically cleaved during apoptosis through the action of DEVD-sensitive caspase(s)...
  48. Roig J, Tuazon P, Zipfel P, Pendergast A, Traugh J. Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK. Proc Natl Acad Sci U S A. 2000;97:14346-51 pubmed
  49. 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 ..
  50. 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 ..
  51. Marlin J, Eaton A, Montano G, Chang Y, Jakobi R. Elevated p21-activated kinase 2 activity results in anchorage-independent growth and resistance to anticancer drug-induced cell death. Neoplasia. 2009;11:286-97 pubmed
    ..As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug-induced apoptosis. ..
  52. Mulle J, Dodd A, McGrath J, Wolyniec P, Mitchell A, Shetty A, et al. Microdeletions of 3q29 confer high risk for schizophrenia. Am J Hum Genet. 2010;87:229-36 pubmed publisher
    ..contains two linkage peaks from prior SZ family studies, and the minimal deletion interval implicates 20 annotated genes, including PAK2 and DLG1, both paralogous to X-linked ID genes and now strong candidates for SZ susceptibility.
  53. Wu H, Wang Z. The mechanism of p21-activated kinase 2 autoactivation. J Biol Chem. 2003;278:41768-78 pubmed
    The p21-activated kinases (PAKs) play an important role in diverse cellular processes. PAK2 is activated by autophosphorylation upon binding of small G proteins such as Cdc42 and Rac in the GTP-bound state...
  54. Mann J, Patrick C, Cragg M, Honeychurch J, Mann D, Harris M. Functional analysis of HIV type 1 Nef reveals a role for PAK2 as a regulator of cell phenotype and function in the murine dendritic cell line, DC2.4. J Immunol. 2005;175:6560-9 pubmed
    ..studies had shown that these mutations also abolished the ability of Nef to activate the p21-activated kinase, PAK2. Consistent with this, stable expression of constitutively active PAK2 in DC2.4 mimicked the effects of Nef...
  55. Lee J, Wittki S, Br u T, Dreyer F, Kr tzel K, Dindorf J, et al. HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Mol Cell. 2013;49:668-79 pubmed publisher
    ..Peripheral blood mononuclear cells that ingested these EVs released TNF?. Analyzing the mechanism, we found that Pak2, an established host cell effector of Nef, phosphorylated paxillin on Ser272/274 to induce TACE-paxillin ..
  56. Gopal S, Greening D, Hanssen E, Zhu H, Simpson R, Mathias R. Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells. Oncotarget. 2016;7:19709-22 pubmed publisher
    ..21D1 exosomes contained VEGF-associated proteins, while MDCKYBX1 exosomes were enriched with activated Rac1 and PAK2. To validate, 2F-2B cells and HUVECs were pre-treated with PAK inhibitors prior to exosome supplementation...
  57. Gavillet M, Martinod K, Renella R, Wagner D, Williams D. A key role for Rac and Pak signaling in Neutrophil Extracellular Traps (NETs) formation defines a new potential therapeutic target. Am J Hematol. 2017;: pubmed publisher
    ..We validated the importance of Pak using Pak2?/? PMNs, which demonstrated significantly impaired histone H3 citrullination and NETosis...
  58. Hiipakka M, Huotari P, Manninen A, Renkema G, Saksela K. Inhibition of cellular functions of HIV-1 Nef by artificial SH3 domains. Virology. 2001;286:152-9 pubmed
    ..Thus, RT-loop-modified SH3 domains represent a novel approach for selectively interfering with cellular signaling events, which could be exploited in research as well as in therapeutic applications. ..
  59. Saxena S, Shrivastava G, Tiwari S, Nair M. HIV-1 Nef: hacker of the host cell. Future Virol. 2012;7:117-120 pubmed
  60. Flate E, Stalvey J. Motility of select ovarian cancer cell lines: effect of extra-cellular matrix proteins and the involvement of PAK2. Int J Oncol. 2014;45:1401-11 pubmed publisher
    ..Involvement of p21?activated kinase 2 (Pak2) in the motility of these cell lines was investigated using a chemical inhibitor as well as siRNA transfection...
  61. Eron S, Raghupathi K, Hardy J. Dual Site Phosphorylation of Caspase-7 by PAK2 Blocks Apoptotic Activity by Two Distinct Mechanisms. Structure. 2017;25:27-39 pubmed publisher
    ..During dysregulation, PAK2 kinase plays an alternative anti-apoptotic role, phosphorylating caspase-7 and promoting unfettered cell growth ..
  62. Alves M, Fuhler G, Queiroz K, Scholma J, Goorden S, Anink J, et al. PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex. Sci Rep. 2015;5:14534 pubmed publisher
    ..of wild-type and Tsc2(-/-) mouse embryonic fibroblasts (MEFs) were generated, revealing a prominent role for PAK2 in signal transduction downstream of TSC1/2...
  63. 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...