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Science 15 May 1998:
Vol. 280. no. 5366, pp. 1082 - 1086
DOI: 10.1126/science.280.5366.1082
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Reports

RasGRP, a Ras Guanyl Nucleotide- Releasing Protein with Calcium- and Diacylglycerol-Binding Motifs

Julius O. Ebinu, Drell A. Bottorff, Edmond Y. W. Chan, Stacey L. Stang, Robert J. Dunn, James C. Stone *

RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of "EF hands" that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.

J. O. Ebinu, D. A. Bottorff, E. Y. W. Chan, S. L. Stang, J. C. Stone, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
R. J. Dunn, Center for Research in Neuroscience, Montreal General Hospital Research Institute, Montreal, Quebec, Canada H3G 1A4.
*   To whom correspondence should be addressed. E-mail: jim.stone{at}ualberta.ca

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   Abstract »    Full Text »    PDF »
Insider Information: How Palmitoylation of Ras Makes It a Signaling Double Agent.
L. G. Berthiaume (2002)
Sci. STKE 2002, pe41
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Calmodulin Prevents Activation of Ras by PKC in 3T3 Fibroblasts.
P. Villalonga, C. Lopez-Alcala, A. Chiloeches, J. Gil, R. Marais, O. Bachs, and N. Agell (2002)
J. Biol. Chem. 277, 37929-37935
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Activation of Ras/Erk Pathway by a Novel MET-interacting Protein RanBPM.
D. Wang, Z. Li, E. M. Messing, and G. Wu (2002)
J. Biol. Chem. 277, 36216-36222
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RasGRP4 Is a Novel Ras Activator Isolated from Acute Myeloid Leukemia.
G. W. Reuther, Q. T. Lambert, J. F. Rebhun, M. A. Caligiuri, L. A. Quilliam, and C. J. Der (2002)
J. Biol. Chem. 277, 30508-30514
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Regulation of T Cell Receptor-induced Activation of the Ras-ER