BetaPix-a enhances the activity of phospholipase Cgamma1 by binding SH3 domain in breast cancer

J Cell Biochem. 2005 Apr 1;94(5):1010-6. doi: 10.1002/jcb.20357.

Abstract

Phospholipase C-gamma1 (PLCgamma1) plays a critical role in cell growth and proliferation by generating the second messengers, diacylglycerol and 1, 4, 5-inositol triphosphate. To investigate the roles of Src homology domain 2 and domain 3 of PLCgamma1 in PLCgamma1-mediated cell signaling, we characterized some proteins binding to these domains in the MCF7 and MDA-MB-231 breast cancer cell lines. Of the several proteins that bind to glutathione-S-transferase-SH2/SH2/SH3, we identified an 85 kDa protein that binds to the SH3 domain of PLCgamma1 as the guanine nucleotide exchange factor, p21-activated protein kinase-interacting exchange factor-a (betaPix-a). BetaPix-a co-immunoprecipitated with PLCgamma1 in breast cancer tissues extracts and in MCF7 and MDA-MB-231 cell extracts. In addition, PDGF-stimulated PLCgamma1 activity was elevated in betaPix-a-overexpressing NIH3T3 cells. Our results suggest that betaPix-a binds to the Src homology domain 3 of PLCgamma1 and promotes tumor growth in breast cancer by enhancing the activity PLCgamma1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / physiology*
  • Female
  • Guanine Nucleotide Exchange Factors / physiology*
  • Humans
  • Hydrolysis
  • Immunohistochemistry
  • Mice
  • NIH 3T3 Cells
  • Phospholipase C gamma
  • Protein Binding
  • Rho Guanine Nucleotide Exchange Factors
  • Type C Phospholipases / metabolism*
  • src Homology Domains

Substances

  • Arhgef7 protein, mouse
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Rho Guanine Nucleotide Exchange Factors
  • Type C Phospholipases
  • Phospholipase C gamma