Inhibition of EGF-dependent calcium influx by annexin VI is splice form-specific.
Annexin VI is a widely expressed calcium- and phospholipid-binding protein that lacks a clear physiological role. We now report that A431 cells expressing annexin VI are defective in their ability to sustain elevated levels of cytosolic Ca(2+) following stimulation with EGF. Other aspects of EGF receptor signaling, such as protein tyrosine phosphorylation and induction of c-fos are normal in these cells. However, EGF-mediated membrane hyperpolarization is attenuated and Ca(2+) entry abolished in cells expressing annexin VI. This effect of annexin VI was only observed for the larger of the two annexin VI splice forms, the smaller splice variant had no discernable effect on either cellular phenotype or growth rate. Inhibition of Ca(2+) influx was specific for the EGF-induced pathway; capacitative Ca(2+) influx initiated by emptying of intracellular stores was unaffected. These results provide the first evidence that the two splice forms of annexin VI have different functions.
Department of Physiology, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
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Fleet
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Ashworth
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Kubista
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Edwards
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Bolsover
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Mobbs
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Moss
D017317:Annexin A6 / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D017136:Ion Transport; D008564:Membrane Potentials / Q000187:drug effects
D017317:Annexin A6; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D002118:Calcium