RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs

Science. 1998 May 15;280(5366):1082-6. doi: 10.1126/science.280.5366.1082.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Catalysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Size
  • Cell Transformation, Neoplastic
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Diglycerides / metabolism
  • Genes, ras
  • Guanine Nucleotide Exchange Factors*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Molecular Sequence Data
  • Neurons / metabolism
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • ras Proteins / metabolism*
  • ras-GRF1

Substances

  • Cell Cycle Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • Diglycerides
  • Guanine Nucleotide Exchange Factors
  • Rasgrp1 protein, rat
  • Recombinant Fusion Proteins
  • ras-GRF1
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • ras Proteins
  • Calcium

Associated data

  • GENBANK/AF060819