PAK2 - Serine/threonine-protein kinase PAK 2 - human protein (Function)
 
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PAK2 »  Serine/threonine-protein kinase PAK 2   [ EC 2.7.11.1 ]
 
Protein also known as:  p21-activated kinase 2 (PAK-2). Cleaved into:  PAK-2p27; PAK-2p34.
Gene name:  PAK2
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

 show evidences
Overview 
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Protein bindingdefinition[GO:0005515]  
13
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • TASPINC
Protein kinase bindingdefinition[GO:0019901]  
1
  • IPIBHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDAMGI
  • IDABHF-UCL
Protein tyrosine kinase activator activitydefinition[GO:0030296]  
1
  • IDABHF-UCL
GO biological process 
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosisdefinition[GO:2001271]  
1
  • IDAUniProtKB
Negative regulation of protein kinase activitydefinition[GO:0006469]  
1
  • TASPINC
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Phosphorylationdefinition[GO:0016310]  
1
  • IDAUniProtKB
Positive regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001238]  
1
  • IMPUniProtKB
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • IDABHF-UCL
Positive regulation of protein tyrosine kinase activitydefinition[GO:0061098]  
1
  • IDAGOC
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAMGI
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAMGI
Regulation of growthdefinition[GO:0040008]  
  • IEAUniProtKB KW
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Signal transduction by phosphorylationdefinition[GO:0023014] silver  
  • IBARefGenome
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.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-402 and allows the kinase domain to adopt an active structure (By similarity). Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Axon guidance  hsa04360+5062  
ErbB signaling pathway  hsa04012+5062  
Focal adhesion  hsa04510+5062  
MAPK signaling pathway  hsa04010+5062  
Regulation of actin cytoskeleton  hsa04810+5062  
Renal cell carcinoma  hsa05211+5062  
T cell receptor signaling pathway  hsa04660+5062  
According to Reactome, this protein belongs to the following pathways:
Activation of Rac  REACT_19226  
CD28 dependent Vav1 pathway  REACT_19238  
FCERI mediated MAPK activation  REACT_163701  
Generation of second messenger molecules  REACT_12623  
Nef and signal transduction  REACT_11068  
Regulation of activated PAK-2p34 by proteasome mediated degradation  REACT_13464  
Regulation of PAK-2p34 activity by PS-GAP/RHG10  REACT_13528  
Sema3A PAK dependent Axon repulsion  REACT_19236  
Stimulation of the cell death response by PAK-2p34  REACT_13532  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Growth regulation  definition   [KW-0341]
Host-virus interaction  definition   [KW-0945]
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: PAK2
GenomeRNAi: 5062
PRO: PR:Q13177
Chemistry
GuidetoPHARMACOLOGY: 2134