RasGRP links T-cell receptor signaling to Ras

Julius Ebinu, Stacey L. Stang, Christine Teixeira, Drell A. Bottorff, Jonathan Hooton, Peter M. Blumberg, Michele Barry, R. Chris Bleakley, Hanne L. Ostergaard, James C. Stone

Research output: Contribution to journalArticle

253 Scopus citations

Abstract

Stimulation of the T-cell receptor (TCR) alters a number of intracellular signaling pathways including one that involves protein tyrosine kinases, phospholipase C-γ1 (PLC-γ1), diacylglycerol (DAG), and calcium messengers. By a divergent pathway, TCR-stimulated protein tyrosine kinase activity is thought to result independently in recruitment of the Ras activator Sos to the plasma membrane, leading to Ras activation. Here we show that RasGRP, a Ras activator that contains calcium-binding EF hands and a DAG-binding domain, is expressed in T cells. A PLC-γ1 inhibitor diminished activation of Ras following TCR stimulation. Membranes from TCR-stimulated Jurkat T cells exhibited increased RasGRP and increased Ras-guanyl nucleotide association activity that was inhibited by antibodies directed against RasGRP. Overexpression of RasGRp in T cells enhanced TCR-Ras-Erk signaling and augmented interleukin-2 secretion in response to calcium ionophore plus DAG analogues phorbol ester myristate or bryostatin-1. Thus, RasGRP links TCR and PLC-γ1 to Ras-Erk signaling, a pathway amenable to pharmacologic manipulation. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)3199-3203
Number of pages5
JournalBlood
Volume95
Issue number10
StatePublished - May 15 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ebinu, J., Stang, S. L., Teixeira, C., Bottorff, D. A., Hooton, J., Blumberg, P. M., Barry, M., Bleakley, R. C., Ostergaard, H. L., & Stone, J. C. (2000). RasGRP links T-cell receptor signaling to Ras. Blood, 95(10), 3199-3203.