Inhibition of EGF-dependent calcium influx by annexin VI is splice form-specific

Annexin VI is a widely expressed calcium and phospholipid-binding protein t hat lacks a clear physiological role. We now report that A431 cells express ing annexin VI are defective in their ability to sustain elevated levels of cytosolic Ca2+ following stimulation with EGF. Other aspects of EGF recept or signaling, such as protein tyrosine phosphorylation and induction of c-f os are normal in these cells. However, EGF-mediated membrane hyperpolarizat ion is attenuated and Ca2+ entry abolished in cells expressing annexin VI. This effect of annexin VI was only observed for the larger of the two annex in VI splice forms, the smaller splice variant had no discernable effect on either cellular phenotype or growth rate. Inhibition of Ca2+ in-flux was s pecific for the EGF-induced pathway; capacitative Ca2+ 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 funct ions. (C) 1999 Academic Press.