Relationship Between Pak-Mediated Cell Death and Stress-Activated Kinase Signaling Breast Cancer
Abstract
Caspase-mediated cleavage of PAK2 is a hallmark of the apoptotic response accompanied by strong JNK activation. The purpose of this study is to characterize the PAK-JNK signaling pathway and to identity% signaling components mediating the JNK activation. In this study we isolated and identified a substrate of p21 -activated kinase PAK which might be a downstream regulator in signaling to the Stress-activated kinase module (SAPK) and the morphological response observed in cells undergoing apoptosis. Peptide mass fingerprinting and immunological methods identified this protein as the guanine nucleotide exchange factor GEF-Hl/K1AAO651. GEF- H1 is strongly phosphorylated by PAK. The phosphorylation site was identified using deletion mapping, phosphopeptide/-amino acid analysis and in vitro mutagenesis. The central dbl-homology domain of the exchange factor mediates strong JNK activation, which seems not to be mediated by the known SAPK-regulatory GTPases Rac and Cdc42. Using in vitro exchange factor assays we observe activation of RhoA, but not Raci. Currently, we test the hypothesis of PAK mediating JNK activation via GEF-H1 and RhoGTPases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2001
- Accession Number
- ADB267683
Entities
People
- Frank T. Zenke
Organizations
- Scripps Research