PAK1 - Serine/threonine-protein kinase PAK 1 - human protein (Function)
 
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PAK1 »  Serine/threonine-protein kinase PAK 1   [ EC 2.7.11.1 ]
 
Protein also known as:  p21-activated kinase 1 (PAK-1).
Gene name:  PAK1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 233 2
GENE REF ISO

Function

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Overview 
Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation.  
17
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Collagen bindingdefinition[GO:0005518]  
1
  • IPIUniProtKB
Contributes to protein bindingdefinition[GO:0005515]  
32
  • IPIIntAct
  • IPIUniProtKB
  • IPIRoslin_Institute
Protein kinase activitydefinition[GO:0004672]  
2
  • IDAUniProtKB
Protein kinase bindingdefinition[GO:0019901] silver  
  • IEAOrtholog Compara
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDAUniProtKB
Receptor signaling protein serine/threonine kinase activitydefinition[GO:0004702] silver  
  • IBARefGenome
GO biological process 
Actin cytoskeleton reorganizationdefinition[GO:0031532]  
2
  • IMPUniProtKB
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Axonogenesisdefinition[GO:0007409] silver  
  • IBARefGenome
Branching morphogenesis of an epithelial tubedefinition[GO:0048754]  
1
  • IMPUniProtKB
Cellular response to insulin stimulusdefinition[GO:0032869] silver  
  • IEAOrtholog Compara
Dendrite developmentdefinition[GO:0016358] silver  
  • IEAOrtholog Compara
Exocytosisdefinition[GO:0006887]  
  • IEAUniProtKB KW
Not  MAPK cascadedefinition[GO:0000165]  
1
  • IDAUniProtKB
Not  Mitotic cell cycledefinition[GO:0000278] silver  
  • IBARefGenome
Negative regulation of cell proliferation involved in contact inhibitiondefinition[GO:0060244]  
1
  • IMPUniProtKB
Neuromuscular junction developmentdefinition[GO:0007528] silver  
  • IEAOrtholog Compara
Neuron projection morphogenesisdefinition[GO:0048812]  
  • ISSOrtholog Curator
Positive regulation of intracellular estrogen receptor signaling pathwaydefinition[GO:0033148]  
1
  • IDAUniProtKB
Positive regulation of JUN kinase activitydefinition[GO:0043507]  
1
  • IMPUniProtKB
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
1
  • IDAUniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IMPUniProtKB
Positive regulation of stress fiber assemblydefinition[GO:0051496]  
1
  • IMPUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Receptor clusteringdefinition[GO:0043113] silver  
  • IEAOrtholog Compara
Response to hypoxiadefinition[GO:0001666] silver  
  • IEAOrtholog Compara
Signal transduction by phosphorylationdefinition[GO:0023014] silver  
  • IBARefGenome
Wound healingdefinition[GO:0042060]  
1
  • IMPUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
3
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
  • CuratedUniProtKB
It is regulated in the following manner
Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423.  
4
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Axon guidance  hsa04360+5058  
Chemokine signaling pathway  hsa04062+5058  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+5058  
ErbB signaling pathway  hsa04012+5058  
Fc gamma R-mediated phagocytosis  hsa04666+5058  
Focal adhesion  hsa04510+5058  
MAPK signaling pathway  hsa04010+5058  
Natural killer cell mediated cytotoxicity  hsa04650+5058  
Regulation of actin cytoskeleton  hsa04810+5058  
Renal cell carcinoma  hsa05211+5058  
T cell receptor signaling pathway  hsa04660+5058  
According to Reactome, this protein belongs to the following pathways:
Cell-Cell communication  REACT_111155  
Developmental Biology  REACT_111045  
Immune System  REACT_6900  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Exocytosis  definition   [KW-0268]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Allosteric enzyme  definition   [KW-0021]
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PAK1
GenomeRNAi: 5058
PRO: PR:Q13153
Chemistry
GuidetoPHARMACOLOGY: 2133