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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ebinu, J. O. Articles by Stone, J. C. Search for Related Content PubMed PubMed Citation Articles by Ebinu, J. O. Articles by Stone, J. C. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 95 No. 10 (May 15), 2000: pp. 3199-3203 RasGRP links T-cell receptor signaling to Ras Julius O. Ebinu, Stacey L. Stang, Christine Teixeira, Drell A. Bottorff, Jonathan Hooton, Peter M. Blumberg, Michele Barry, R. Chris Bleakley, Hanne L. Ostergaard, and James C. Stone From the Departments of Biochemistry and Immunobiology, University of Alberta, Edmonton, Alberta, Canada; and the Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD. Stimulation of the T-cell receptor (TCR) alters a number of intracellular signaling pathways including one that involves protein tyrosine kinases, phospholipase C-1 (PLC-1), 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-1 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-1 to Ras-Erk signaling, a pathway amenable to pharmacologic manipulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. J. Botelho, R. E. Harrison, J. C. Stone, J. F. Hancock, M. R. Philips, J. Jongstra-Bilen, D. Mason, J. Plumb, M. R. Gold, and S. Grinstein Localized Diacylglycerol-dependent Stimulation of Ras and Rap1 during Phagocytosis J. Biol. Chem., October 16, 2009; 284(42): 28522 - 28532. [Abstract] [Full Text] [PDF] M. Miyaji, R. L. Kortum, R. Surana, W. Li, K. D. Woolard, R. M. 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