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

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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.  
9
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
1
  • IntAct
Protein bindingdefinition[GO:0005515]  
14
  • IntAct
  • UniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • PINC
Protein kinase bindingdefinition[GO:0019901]  
1
  • BHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • MGI
  • BHF-UCL
Protein tyrosine kinase activator activitydefinition[GO:0030296]  
1
  • BHF-UCL
Rac GTPase bindingdefinition[GO:0048365]  
1
  • RefGenome
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036]  
1
  • RefGenome
Activation of protein kinase activitydefinition[GO:0032147]  
1
  • RefGenome
Cell migrationdefinition[GO:0016477]  
1
  • RefGenome
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • UniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosisdefinition[GO:2001271]  
1
  • UniProtKB
Negative regulation of protein kinase activitydefinition[GO:0006469]  
1
  • PINC
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • BHF-UCL
Phosphorylationdefinition[GO:0016310]  
1
  • UniProtKB
Positive regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001238]  
1
  • UniProtKB
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • BHF-UCL
Positive regulation of protein tyrosine kinase activitydefinition[GO:0061098]  
1
  • GOC
Protein autophosphorylationdefinition[GO:0046777]  
1
  • MGI
Protein phosphorylationdefinition[GO:0006468]  
1
  • MGI
Regulation of growthdefinition[GO:0040008]  
1
  • UniProtKB KW
Regulation of MAPK cascadedefinition[GO:0043408]  
1
  • RefGenome
Regulation of mitotic cell cycledefinition[GO:0007346]  
1
  • RefGenome
Rho protein signal transductiondefinition[GO:0007266]  
1
  • RefGenome
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Signal transduction by protein phosphorylationdefinition[GO:0023014]  
1
  • RefGenome
Stress-activated protein kinase signaling cascadedefinition[GO:0031098]  
1
  • RefGenome
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.  
1
  • UniProtKB
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.  
1
  • UniProtKB
 
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  R-HSA-428540  
CD209 (DC-SIGN) signaling  R-HSA-5621575  
CD28 dependent Vav1 pathway  R-HSA-389359  
Ephrin signaling  R-HSA-3928664  
FCERI mediated MAPK activation  R-HSA-2871796  
Generation of second messenger molecules  R-HSA-202433  
MAPK6/MAPK4 signaling  R-HSA-5687128  
Nef and signal transduction  R-HSA-164944  
Regulation of activated PAK-2p34 by proteasome mediated degradation  R-HSA-211733  
Regulation of PAK-2p34 activity by PS-GAP/RHG10  R-HSA-211728  
RHO GTPases activate PAKs  R-HSA-5627123  
Sema3A PAK dependent Axon repulsion  R-HSA-399954  
Stimulation of the cell death response by PAK-2p34  R-HSA-211736  
VEGFA-VEGFR2 Pathway  R-HSA-4420097  
VEGFR2 mediated vascular permeability  R-HSA-5218920  
 

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