title: RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
authors.forename: J O
authors.initials: JO
authors.lastname: Ebinu
authors.forename: D A
authors.initials: DA
authors.lastname: Bottorff
authors.forename: E Y
authors.initials: EY
authors.lastname: Chan
authors.forename: S L
authors.initials: SL
authors.lastname: Stang
authors.forename: R J
authors.initials: RJ
authors.lastname: Dunn
authors.forename: J C
authors.initials: JC
authors.lastname: Stone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002384:Catalysis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D011905:Genes, ras; D020662:Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*; D020666:ras-GRF1
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004075:Diglycerides; D020662:Guanine Nucleotide Exchange Factors; C491789:Rasgrp1 protein, rat; D011993:Recombinant Fusion Proteins; D020666:ras-GRF1; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D018631:ras Proteins; D002118:Calcium