RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration

J Cell Biol. 2006 Sep 11;174(6):877-88. doi: 10.1083/jcb.200603111.

Abstract

The Ras family of small GTPases regulates cell proliferation, spreading, migration and apoptosis, and malignant transformation by binding to several protein effectors. One such GTPase, R-Ras, plays distinct roles in each of these processes, but to date, identified R-Ras effectors were shared with other Ras family members (e.g., H-Ras). We utilized a new database of Ras-interacting proteins to identify RLIP76 (RalBP1) as a novel R-Ras effector. RLIP76 binds directly to R-Ras in a GTP-dependent manner, but does not physically associate with the closely related paralogues H-Ras and Rap1A. RLIP76 is required for adhesion-induced Rac activation and the resulting cell spreading and migration, as well as for the ability of R-Ras to enhance these functions. RLIP76 regulates Rac activity through the adhesion-induced activation of Arf6 GTPase and activation of Arf6 bypasses the requirement for RLIP76 in Rac activation and cell spreading. Thus, we identify a novel R-Ras effector, RLIP76, which links R-Ras to adhesion-induced Rac activation through a GTPase cascade that mediates cell spreading and migration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / metabolism
  • Animals
  • Cell Adhesion / physiology
  • Cell Movement / physiology*
  • Cell Size
  • Fibroblasts / metabolism
  • Fibroblasts / ultrastructure
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Guanosine Triphosphate / metabolism
  • Mice
  • NIH 3T3 Cells
  • Protein Binding / physiology
  • Signal Transduction / physiology
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • GTPase-Activating Proteins
  • Ralbp1 protein, mouse
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • Rras protein, mouse
  • ADP-Ribosylation Factors
  • ADP-ribosylation factor 6
  • rac GTP-Binding Proteins
  • ras Proteins