Catalytic activity:ATP + a protein = ADP + a phosphoprotein. ,enzyme regulation: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 , autophosphorylted PAK-2p34 is constitutively active. ,Function:The activated kinase acts on a variety of targets. Phosphorylates ribosomal protein S6 , histone H4 and myelin basic protein. Full length PAK 2 stimulates cell survival and cell growth. The process is , at least in part , mediated by phosphorylation and inhibition of pro-apoptotic BAD. Caspase-activated PAK-2p34 is involved in cell death response , probably involving the JNK signaling pathway. Cleaved PAK-2p34 seems to have a higher activity than the CDC42-activated form. ,PTM:During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34. ,PTM:Full length PAK 2 is autophosphorylated when activated by CDC42/p21. Following cleavage , both peptides , PAK-2p27 and PAK-2p34 , become highly autophosphorylated , with PAK-2p27 being phosphorylated on serine and PAK-2p34 on threonine residues , respectively. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402 , because PAK-2p27 is acting as an exogenous substrate. ,PTM:PAK-2p34 is myristoylated. ,PTM:Ubiquitinated , leading to its proteosomal degradation. ,similarity:Belongs to the protein kinase superfamily. ,similarity:Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. ,similarity:Contains 1 CRIB domain. ,similarity:Contains 1 protein kinase domain. ,subcellular location:Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region. Myristoylation changes PAK-2p34 location to the membrane. ,subunit:Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with and activated by HIV-1 Nef. PAK-2p34 interacts with ARHGAP10. ,tissue specificity:Ubiquitously expressed. Higher levels seen in skeletal muscle , ovary , thymus and spleen. ,
展开内容