Stimulation of the cell death response by PAK-2p34

Stable Identifier
R-HSA-211736
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

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).

Literature References
PubMed ID Title Journal Year
15234964 Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk

Orton, KC, Ling, J, Waskiewicz, AJ, Cooper, JA, Merrick, WC, Korneeva, NL, Rhoads, RE, Sonenberg, N, Traugh, JA

J Biol Chem 2004
9786869 Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). Effects of autophosphorylation on activity

Walter, BN, Huang, Z, Jakobi, R, Tuazon, PT, Alnemri, ES, Litwack, G, Traugh, JA

J Biol Chem 1998
15471851 Identification and characterization of PS-GAP as a novel regulator of caspase-activated PAK-2

Koeppel, MA, McCarthy, CC, Moertl, E, Jakobi, R

J Biol Chem 2004
12853446 Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation

Jakobi, R, McCarthy, CC, Koeppel, MA, Stringer, DK

J Biol Chem 2003
Participants
Participant Of
Authored
Reviewed
Created