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 activating protein (p120GAP) (Clark et al. Cell 65: 1043-1051, 1991). Here we show the 43 residue CaLB motif in p120GAP is a functional protein domain that when expressed as a fusion protein in vitro confers Ca(2+)-dependent interactions with cellular membranes and phosphatidylserine and phosphatidylinositol vesicles. p120GAP, but not a mutant lacking the CaLB domain, associates with the particulate fraction of cells in response to elevated intracellular Ca2+ suggesting that p120GAP may be regulated in part by calcium signals. Addition of the p120GAP CaLB domain was able to restore transforming activity and particulate localization to an otherwise transformation-defective and cytosolic mutant v-Sre tyrosine kinase. The CaLB domain appears to be a prevalent protein module that may affect the molecular interactions and subcellular localization of signalling proteins.
Gawler
D J
DJ
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Zhang
L J
LJ
Reedijk
M
M
Tung
P S
PS
Moran
M F
MF
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D020690:GTPase-Activating Proteins; D016391:Genes, src; D051379:Mice; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D010743:Phospholipids; D021382:Protein Sorting Signals; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D002118:Calcium