The role of pp60c-src in the regulation of calcium entry via store-operated calcium channels.
In many cell types, G protein-coupled receptors stimulate a transient Ca2+ release from internal stores followed by a sustained, capacitative Ca2+ entry, which is mediated by store-operated channels (SOCs). Although it is clear that SOCs are activated by depletion of internal Ca2+ stores, the mechanism for this process is not well understood. Previously, we have reported that inhibitors of tyrosine kinase activity block the bradykinin- and thapsigargin-stimulated Ca2+ entry in fibroblasts, suggesting that a tyrosine kinase activity may be involved in relaying the message from the empty internal Ca2+ stores to the plasma membrane Ca2+ channel (Lee, K.-M., Toscas, K., and Villereal, M. L. (1993) J. Biol. Chem. 268, 9945-9948). We also have demonstrated that bradykinin activates the nonreceptor tyrosine kinase c-src (Lee, K.-M., and Villereal, M. L. (1996) Am. J. Physiol. 270, C1430-C1437). We investigated whether c-src plays a role in the regulation of SOCs by monitoring capacitative Ca2+ entry in 3T3-like embryonic fibroblast lines derived from either wild type or src-/src- (Src-) transgenic mice. We report that Ca2+ entry, following store depletion by either bradykinin or thapsigargin, is dramatically lower in Src- fibroblasts than in wild type fibroblasts. The level of capacitative Ca2+ entry in Src- cells is restored to nearly normal levels by transfecting Src- cells with chicken c-src. These data suggest that c-src may play a major role in the regulation of SOCs.
Babnigg
G
G
Department of Pharmacological and Physiological Sciences, The University of Chicago, Chicago, Illinois 60637, USA.
Bowersox
S R
SR
Villereal
M L
ML
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels; D051379:Mice; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D019284:Thapsigargin; D016392:Proto-Oncogene Proteins pp60(c-src); D000252:Calcium-Transporting ATPases; D001920:Bradykinin; D002118:Calcium