Relationship between Pak-Mediated Cell Death and Stress-Activated Kinase Signaling in Breast Cancer

Abstract

The identification of the guanine nucleotide exchange factor GEF-H1/KIAA0651 as a substrate of PAK kinases and a mediator of JNK signaling suggested it to be a good candidate for a linker between caspase-mediated Pak2 activation and JNK signaling. As yet, we have no evidence that exchange factor activity is regulated by PAK phosphorylation. Instead, localization of the exchange factor on microtubules may inhibit GEF activity. Studies using microtubule drugs and exchange factor mutants support a model in which RhoA activation through microtubule depolymerization is mediated GEF-H1. In addition, we could show that phosphorylation of GEF-H1/KIAA0651 by Pak recruits 14-3-3 proteins and hypothesize that Pak is involved in regulating protein docking to GEF-H1/KIAA0651.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2002
Accession Number
ADB282231

Entities

People

  • Becky A. Diebold

Organizations

  • Scripps Research

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cell Movement
  • Cell Physiological Processes
  • Cell Shape
  • Cells
  • Computer Programs
  • Cytoskeleton
  • Depolymerization
  • Gene Expression
  • Governments
  • Identification
  • Kinases
  • Neoplasms
  • Proteins

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Biology and Genetics