p21 Protein Activated Kinase 1 (PAK1)

PAKalpha; p65-PAK; p21/Cdc42/Rac1-Activated Kinase 1; Serine/threonine-protein kinase PAK 1

SPN	P266
HGNC	8590
MGI	1339975
PubMed	8805275
RGD	3250
UniProt	Q13153
Wiki	PAK1

PAK proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling. PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK1 regulates cell motility and morphology.

PAK1 is a member of a family of serine/threonine kinases related to yeast Ste20. The human PAK1 gene encodes a 545-amino acid polypeptide that is 98% identical to rat PAK1 and 52% identical to yeast Ste20. Activity of PAK1 is induced by coexpression with RAC1 or CDC42. PAK is believed to act directly on the JNK1 MAP kinase pathway.

Reference

"Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway."
Curr. Biol. 6:598-605(1996) [PubMed] [Europe PMC] [Abstract]

"Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells."
Curr. Biol. 7:202-210(1997) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes."
Mol. Cell. Biol. 17:1129-1143(1997) [PubMed] [Europe PMC] [Abstract]

"Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation."
J. Biol. Chem. 273:28191-28198(1998) [PubMed] [Europe PMC] [Abstract]

"A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1."
Mol. Cell. Biol. 18:2153-2163(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck."
J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity."
J. Biol. Chem. 274:32565-32573(1999) [PubMed] [Europe PMC] [Abstract]

"p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1)."
J. Biol. Chem. 275:41201-41209(2000) [PubMed] [Europe PMC] [Abstract]

"Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1."
J. Biol. Chem. 277:4395-4405(2002) [PubMed] [Europe PMC] [Abstract]

"Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1."
Mol. Cell 9:73-83(2002) [PubMed] [Europe PMC] [Abstract]

"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. 278:20029-20036(2003) [PubMed] [Europe PMC] [Abstract]

"PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation."
J. Cell Biol. 162:281-291(2003) [PubMed] [Europe PMC] [Abstract]

"Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell migration."
Mol. Cell. Biol. 23:8058-8069(2003) [PubMed] [Europe PMC] [Abstract]

"The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak."
J. Biol. Chem. 279:32824-32831(2004) [PubMed] [Europe PMC] [Abstract]

"Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions."
Cancer Res. 65:3179-3184(2005) [PubMed] [Europe PMC] [Abstract]

"Integrin engagement differentially modulates epithelial cell motility by RhoA/ROCK and PAK1."
J. Biol. Chem. 280:10624-10635(2005) [PubMed] [Europe PMC] [Abstract]

"Essential role of CIB1 in regulating PAK1 activation and cell migration."
J. Cell Biol. 170:465-476(2005) [PubMed] [Europe PMC] [Abstract]

"p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B."
Mol. Cell. Biol. 25:3726-3736(2005) [PubMed] [Europe PMC] [Abstract]

"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]

"CRIPak, a novel endogenous Pak1 inhibitor."
Oncogene 25:1311-1319(2006) [PubMed] [Europe PMC] [Abstract]

"JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions."
J. Biol. Chem. 282:30985-30996(2007) [PubMed] [Europe PMC] [Abstract]

"Identification of phosphorylation sites in betaPIX and PAK1."
J. Cell Sci. 120:3911-3918(2007) [PubMed] [Europe PMC] [Abstract]

"Affixin activates Rac1 via betaPIX in C2C12 myoblast."
FEBS Lett. 582:1189-1196(2008) [PubMed] [Europe PMC] [Abstract]

"Scrib regulates PAK activity during the cell migration process."
Hum. Mol. Genet. 17:3552-3565(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic beta-Cells."
J. Biol. Chem. 287:26435-26444(2012) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis."
Oncogene 33:1167-1180(2014) [PubMed] [Europe PMC] [Abstract]

"Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6."
Sci. Signal. 6:RA30-RA30(2013) [PubMed] [Europe PMC] [Abstract]

"Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch."
Cell 102:387-397(2000) [PubMed] [Europe PMC] [Abstract]

"Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK)."
Biochemistry 44:10977-10983(2005) [PubMed] [Europe PMC] [Abstract]

"The active conformation of the PAK1 kinase domain."
Structure 13:769-778(2005) [PubMed] [Europe PMC] [Abstract]

"Structural insights into the autoactivation mechanism of p21-activated protein kinase."
Structure 19:1752-1761(2011) [PubMed] [Europe PMC] [Abstract]