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PAK1 human: p21 protein (Cdc42/Rac)-activated kinase 1

Aliases: p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related), p21-activated kinase 1, STE20 homolog, yeast, p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast), PAKalpha, PAK1, MGC130000, MGC130001

Pfam Domain Structure

From PAK1 (human) - phosphorylation sites added via direct mapping

Protein Overview
Official Gene Name PAK1 (H. sapiens)
RefSeq Protein Name p21 protein (Cdc42/Rac)-activated kinase 1
UniProt Gene Symbol PAK1_HUMAN
UniProt Name Serine/threonine-protein kinase PAK 1
Enzyme Commission 2.7.11.1
Entrez Gene Summary This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]
References
  1. Bokoch GM. Biology of the p21-activated kinases. Annu. Rev. Biochem. 2003; 72:743-81 (PubMed)
  2. Chew TL, Masaracchia RA, Goeckeler ZM, Wysolmerski RB. 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)
  3. Cotteret S, Chernoff J. Pak GITs to Aurora-A. Dev. Cell 2005; 9:573-4 (PubMed)
  4. Dummler B, Ohshiro K, Kumar R, Field J. Pak protein kinases and their role in cancer. Cancer Metastasis Rev. 2009; 28:51-63 (PubMed)
  5. Fryer BH, Field J. Rho, Rac, Pak and angiogenesis: old roles and newly identified responsibilities in endothelial cells. Cancer Lett. 2005; 229:13-23 (PubMed)
  6. Gerthoffer WT. Actin cytoskeletal dynamics in smooth muscle contraction. Can. J. Physiol. Pharmacol. 2005; 83:851-6 (PubMed)
  7. Hoefen RJ, Berk BC. The multifunctional GIT family of proteins. J. Cell. Sci. 2006; 119:1469-75 (PubMed)
  8. Hofmann C, Shepelev M, Chernoff J. The genetics of Pak. J. Cell. Sci. 2004; 117:4343-54 (PubMed)
  9. Howe AK. Regulation of actin-based cell migration by cAMP/PKA. Biochim. Biophys. Acta 2004; 1692:159-74 (PubMed)
  10. Juliano RL, Reddig P, Alahari S, Edin M, Howe A, Aplin A. Integrin regulation of cell signalling and motility. Biochem. Soc. Trans. 2004; 32:443-6 (PubMed)
  11. Labruyère E, Guillén N. Host tissue invasion by Entamoeba histolytica is powered by motility and phagocytosis. Arch. Med. Res. 2006; 37:253-8 (PubMed)
  12. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 1994; 367:40-6 (PubMed)
  13. Parrini MC, Matsuda M, de Gunzburg J. Spatiotemporal regulation of the Pak1 kinase. Biochem. Soc. Trans. 2005; 33:646-8 (PubMed)
  14. Settleman J. PAK-in' up cGMP for the move. Cell 2007; 128:237-8 (PubMed)
  15. Vlahou G, Rivero F. Rho GTPase signaling in Dictyostelium discoideum: insights from the genome. Eur. J. Cell Biol. 2006; 85:947-59 (PubMed)
  16. Zhao ZS, Manser E. PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation. Biochem. J. 2005; 386:201-14 (PubMed)
Consortium Results & Data
Results & Data
Ortholog Species Type Description Method Status Source Publications
PAK1 none binding partner Pak1 Ectopic expression in HEK cells 13 proteins exclusively co-purified with Pak1 Horwitz Mayhew et al.
PAK1 none phosphorylation site Pak1 Ectopic expression in HEK cells 30 phospho-sites in 80.5% coverage of 529 aa Horwitz Mayhew et al.
Discovery» PyMT invasive data
Gene mRNA Description Expression Ratio
Pak1
Entrez Gene: 18479
 mRNA: AA061378
UniGene: Mm.260227
 P21 (CDKN1A)-activated kinase 1 2.01
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK1
Aliases: PAKalpha
Entrez Gene: 5058
siRNA catalog 		p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)
mRNA: NM_002576
Library: Kinase
Classification: Tyr Kinase
Focal Adhesion Related: Yes
 Final bin: Discordant
SMARTpool bin: Low Alamar
Avg area: 2.14
Avg Alamar: 0.79
Knockdown %: 90-100
 ERBB2: Impaired
BCL2: Low Alamar 		PAK1
Link 		PAK1
Link 		 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK1
Aliases: PAKalpha
Entrez Gene: 5058
siRNA catalog 		p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)
mRNA: NM_002576
Library: Kinase
 PAK1
Link 		PAK1
Link
Discovery» Drosophila Migration Genes
Gene Name Function Cell
Type 		Phenotypes Reagents/
Alleles 		Reference
Pak
Entrez: CG10295
Flybase: FBgn0014001 		PAK-kinase protein serine/threonine kinase activity dorsal closure Loss of function: dorsal closure defects
Autonomous: Both amnioserosa and epidermis 		Pak20, PakAID (autoinhibitory domain of dPak) Conder, 2004
Discovery» Drosophila Morphology Genes
Gene Name Cell Count/
Normalization 		Stellate11
NumCorners 		Stellate22
Binsum6 		Non-Spreading3
CG10295
Entrez Gene: 44039
 PAK-kinase
Aliases: Pak1 kinase; p21-associated kinase; p-21 activated kinase; p21-activated kinase; Pak kinase; PAK kinase; p21-activated serine/threonine kinase 		10.125
1.138 		0.99 0.989 Actin: 0.871
Area: 0.948
Ratio: 0.919
Isoforms
Isoform Name RefSeq Protein RefSeq mRNA Swissprot ID
isoform 2 NP_002567 NM_002576 Q13153-1
isoform 1 NP_001122092 NM_001128620 Q13153-2

bold indicates the primary isoform

Pathways

How many degrees of interaction?

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Legend: Legend for CMKB pathways