Editors' ChoiceCell Biology

Calcium Signals Stop Through CAPRI

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Science's STKE  03 Jul 2001:
Vol. 2001, Issue 89, pp. tw6
DOI: 10.1126/stke.2001.89.tw6

Lockyer et al. have identified and characterized a new member of the Ras guanosine triphosphatase (GTPase)-activating protein (GAP) family that is regulated by calcium and thus, named Ca2+-promoted Ras activator (CAPRI). Capri has structural similarity (a pleckstrin homology domain, a GAP-related domain, and a Bruton's tyrosine kinase motif) to members of the Ras GAP1 subfamily, but unlike other members of the subfamily, CAPRI has functional calcium-binding C2 domains. The redistribution of CAPRI to the plasma membrane in transfected cells was stimulated by increases in intracellular Ca2+ (either by treatment with a calcium ionophore or activation of the purinergic G protein-coupled receptor that activates phospholipase C leading to increased intracellular Ca2+ owing to production of inositol trisphosphate). Unlike other members of the GAP1 family, CAPRI was not sensitive to changes in phosphatidylinositol lipids in the membrane. Increases in intracellular Ca2+ were required to activate the GAP activity of CAPRI. In transfected cells, activation of CAPRI attenuated calcium-induced activation of the Ras-mitogen-activated protein kinase (MAPK) pathway. Expression of a dominant negative form of CAPRI enhanced phosphorylation of the MAPKs ERK1 and ERK2. Thus, CAPRI may be an off switch that helps to regulate the output of calcium-mediated activation of the Ras-MAPK pathway.

P. J. Lockyer, S. Kupzig, P. J. Cullen, CAPRI regulates the Ca2+-dependent inactivation of the Ras-MAPK pathway. Current Biol. 11, 981-986 (2001). [Full Text]

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