Rac2 Stimulates Akt Activation Affecting BAD/Bcl-XL Expression While Mediating Survival and Actin Function in Primary Mast Cells

Immunity. 2000 May;12(5):557-68. doi: 10.1016/s1074-7613(00)80207-1.

Abstract

Mast cells generated from Rac2-deficient (-/-) mice demonstrated defective actin-based functions, including adhesion, migration, and degranulation. Rac2(-/-) mast cells generated lower numbers and less mast cell colonies in response to growth factors and were deficient in vivo. Rac2(-/-) mast cells demonstrated a significant reduction in growth factor-induced survival, which correlated with the lack of activation of Akt and significant changes in the expression of the Bcl-2 family members BAD and Bcl-XL, in spite of a 3-fold induction of Rac1 protein. These results suggest that Rac2 plays a unique role in multiple cellular functions and describe an essential role for Rac2 in growth factor-dependent survival and expression of BAD/Bcl-XL.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation
  • Mast Cells / metabolism*
  • Mast Cells / pathology
  • Mice
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • bcl-Associated Death Protein
  • rac GTP-Binding Proteins / deficiency*
  • rac GTP-Binding Proteins / genetics

Substances

  • Actins
  • Bad protein, mouse
  • Carrier Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-Associated Death Protein
  • Protein-Serine-Threonine Kinases
  • rac2 GTP-binding protein
  • rac GTP-Binding Proteins