Inhibition by calyculin A and okadaic acid of the Ca(2+) release-activated Ca(2+) entry pathway in rat basophilic leukemia cells: evidence for regulation by type 1/2A serine/threonine phosphatase activity.
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| Abstract |
Using a combination of fluorescence measurements of intracellular Ca(2+) ion concentration ([Ca(2+)](i)) and membrane potential we have investigated the sensitivity to serine/threonine phosphatase inhibition of Ca(2+) entry stimulated by activation of the Ca(2+) release-activated Ca(2+) (CRAC) entry pathway in rat basophilic leukemia cells. In both suspension and adherent cells, addition of the type 1/2A phosphatase inhibitor calyculin A, during activation of CRAC uptake, resulted in a fall in [Ca(2+)](i) to near preactivation levels. Pre-treatment with calyculin A abolished the component of the Ca(2+) rise associated with activation of CRAC uptake and inhibited Mn(2+) entry, consistent with a requirement of phosphatase activity for activation of the pathway. Depletion of intracellular Ca(2+) stores is accompanied by a large depolarisation which is absolutely dependent upon Ca(2+) entry via the CRAC uptake pathway. Application of calyculin A or okadaic acid, a structurally unrelated phosphatase antagonist inhibits this depolarisation. Taken in concert, these data demonstrate a marked sensitivity of the CRAC entry pathway to inhibition by calyculin A and okadaic acid.
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| Authors | Nicholas E Evans, Mark K L Forth, Anna K Simpson, Michael J Mason |
| Journal | Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1718 Issue 1-2 Pg. 32-43 (Dec 10 2005) ISSN: 0006-3002 [Print] Netherlands |
| PMID | 16297373 (Publication Type: Journal Article) |
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