Requirement for Ras guanine nucleotide releasing protein 3 in coupling phospholipase C-gamma2 to Ras in B cell receptor signaling

J Exp Med. 2003 Dec 15;198(12):1841-51. doi: 10.1084/jem.20031547.

Abstract

Two important Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and Ras guanine nucleotide releasing protein (RasGRP), have been implicated in controlling Ras activation when cell surface receptors are stimulated. To address the specificity or redundancy of these exchange factors, we have generated Sos1/Sos2 double- or RasGRP3-deficient B cell lines and determined their ability to mediate Ras activation upon B cell receptor (BCR) stimulation. The BCR requires RasGRP3; in contrast, epidermal growth factor receptor is dependent on Sos1 and Sos2. Furthermore, we show that BCR-induced recruitment of RasGRP3 to the membrane and the subsequent Ras activation are significantly attenuated in phospholipase C-gamma2-deficient B cells. This defective Ras activation is suppressed by the expression of RasGRP3 as a membrane-attached form, suggesting that phospholipase C-gamma2 regulates RasGRP3 localization and thereby Ras activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Guanine Nucleotide Exchange Factors / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Phospholipase C gamma
  • Receptors, Antigen, B-Cell / physiology*
  • SOS1 Protein / physiology
  • Signal Transduction
  • Son of Sevenless Proteins / physiology
  • Type C Phospholipases / physiology*
  • ras Guanine Nucleotide Exchange Factors
  • ras Proteins / physiology*

Substances

  • Guanine Nucleotide Exchange Factors
  • RASGRP3 protein, human
  • Receptors, Antigen, B-Cell
  • SOS1 Protein
  • SOS2 protein, human
  • Son of Sevenless Proteins
  • Sos2 protein, mouse
  • ras Guanine Nucleotide Exchange Factors
  • Type C Phospholipases
  • Phospholipase C gamma
  • ras Proteins