CALB - A 43 AMINO-ACID CALCIUM-DEPENDENT MEMBRANE PHOSPHOLIPID-BINDING DOMAIN IN P120 RAS GTPASE-ACTIVATING PROTEIN

CaLB was originally observed as a conserved sequence motif in various calcium-responsive signalling proteins and also in p120 Ras GTPase act ivating protein (p120(GAP)) (Clark et al. Cell 65: 1043-1051, 1991). H ere we show the 43 residue CaLB motif in p120(GAP) is a functional pro tein domain that when expressed as a fusion protein in vitro confers C a2+-dependent interactions with cellular membranes and phosphatidylser ine and phosphatidylinositol vesicles. p120(GAP), but not a mutant lac king the CaLB domain, associates with the particulate fraction of cell s in response to elevated intracellular Ca2+ suggesting that p120(GAP) may be regulated in part by calcium signals. Addition of the p120(GAP ) CaLB domain was able to restore transforming activity and particulat e localization to an otherwise transformation-defective and cytosolic mutant v-Src tyrosine kinase. The CaLB domain appears to be a prevalen t protein module that may affect the molecular interactions and subcel lular localization of signalling proteins.