PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration

Mol Endocrinol. 2009 Jun;23(6):901-13. doi: 10.1210/me.2008-0368. Epub 2009 Mar 5.

Abstract

It is well established that epidermal growth factor (EGF) induces the cytoskeleton reorganization and cell migration through two major signaling cascades: phospholipase C-gamma1 (PLC-gamma1) and Rho GTPases. However, little is known about the cross talk between PLC-gamma1 and Rho GTPases. Here we showed that PLC-gamma1 forms a complex with Rac1 in response to EGF. This interaction is direct and mediated by PLC-gamma1 Src homology 3 (SH3) domain and Rac1 (106)PNTP(109) motif. This interaction is critical for EGF-induced Rac1 activation in vivo, and PLC-gamma1 SH3 domain is actually a potent and specific Rac1 guanine nucleotide exchange factor in vitro. We have also demonstrated that the interaction between PLC-gamma1 SH3 domain and Rac1 play a significant role in EGF-induced F-actin formation and cell migration. We conclude that PLC-gamma1 and Rac1 coregulate EGF-induced cell cytoskeleton remodeling and cell migration by a direct functional interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Movement / drug effects*
  • Chlorocebus aethiops
  • Cytoskeleton / drug effects*
  • Cytoskeleton / metabolism*
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Molecular Sequence Data
  • Phospholipase C gamma / chemistry
  • Phospholipase C gamma / metabolism*
  • Protein Binding / drug effects
  • rac1 GTP-Binding Protein / metabolism*
  • src Homology Domains

Substances

  • Actins
  • Guanine Nucleotide Exchange Factors
  • Epidermal Growth Factor
  • Phospholipase C gamma
  • rac1 GTP-Binding Protein