Abstract
TYROSINE kinase receptors stimulate the Ras signalling pathway by enhancing the activity of the SOS nucleotide-exchange factor1. This occurs, at least in part, by the recruitment of an SOSá¤-GRB2 complex to Ras in the plasma membrane. Here we describe a different signalling pathway to Ras that involves activation of the Ras-GRF exchange factor2á¤-4 in response to Ca2+influx. In particular, we show that the ability of Ras-GRF to activate Ras in vivo is markedly enhanced by raised Ca2+ concentrations. Activation is mediated by calmodulin binding to an IQ motif5 in Ras-GRF, because substitutions in conserved amino acids in this motif prevent both calmodulin binding to Ras-GRF and Ras-GRF activation in vivo. So far, full-length Ras-GRF has been detected only in brain neurons2,6,7. Our findings implicate Ras-GRF in the regulation of neuronal functions that are influenced by Ca2+ signals.
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Farnsworth, C., Freshney, N., Rosen, L. et al. Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF. Nature 376, 524–527 (1995). https://doi.org/10.1038/376524a0
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DOI: https://doi.org/10.1038/376524a0
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