Partial autophosphorylation of PAK-2 at Ser-19, Ser-20, Ser-55, Ser-192, and Ser-197 Proteolytic PAK-2p34 fragment translocates to the nucleus Autophosphorylation of PAK-2p34 in the activation loop Cleavage of PAK-2 at 212 PathwayStep4422 PathwayStep4424 PathwayStep4423 PathwayStep4425 Stimulation of the cell death response by PAK-2p34 Authored: Jakobi, R, 2008-02-05 11:04:14 Edited: Matthews, L, 2008-02-03 20:50:13 Edited: Matthews, L, 2008-06-12 00:23:53 In response to stress signals, the p21-activated protein kinase PAK-2 stimulates a cell death response characterized by increased cell rounding and apoptotic chromatin condensation (see Jakobi et al., 2003). PAK-2 is proteolytically cleaved by caspase-3 producing a constitutively active fragment, PAK-2p34. Following cleavage, PAK-2p34 is autophosphorylated at Thr 402 and transported to the nucleus where it accumulates due to the loss of its nuclear export signal motif (Jakobi et al., 2003). The activity of PAK-2p34 appears to be regulated both by proteosomal degradation (Jakobi et al., 2003) and by association with the GTPase-activating protein PS-GAP/ RHG-10. This interaction inhibits the kinase activity of PAK-2p34 and changes the localization of PAK-2p34 from the nucleus to the perinuclear region (Koeppel et al., 2004). PAK-2p34 may function in the down-regulation of translation initiation in apoptosis through phosphorylation of Mnk1 (Orton et al.,2004). Pubmed12853446 Pubmed15234964 Pubmed15471851 Pubmed9786869 Reactome Database ID Release 43211736 Reactome, http://www.reactome.org ReactomeREACT_13532 Reviewed: Chang, E, 2008-05-21 00:05:41