A 50-kDa integrin-associated protein is required for integrin-regulated calcium entry in endothelial cells.

A 50-kDa integrin-associated protein (IAP), identified by its role in activation of neutrophils by extracellular matrix proteins, has recently been found to have a primary sequence that predicts five transmembrane domains, raising the possibility that the protein participates in ion transport. In endothelial cells, extracellular matrix proteins and anti-integrin antibodies have been shown to trigger an influx of [Ca2+]i via voltage-independent membrane channels. We now show that monoclonal antibodies to IAP that block neutrophil activation completely inhibited the fibronectin-stimulated rise in [Ca2+]i in endothelial cells. An antibody that binds IAP but does not block neutrophil function had no effect on endothelial cell [Ca2+]i. Inhibition of IAP function had no effect on endothelial cell adhesion, no effect on the integrin-mediated rise in intracellular pH, and no effect on the integrin-mediated increase in tyrosine phosphorylation. In addition, inhibition of IAP had no effect on the influx of Ca2+ triggered by histamine. These results demonstrate that IAP is specifically required for the integrin-regulated calcium influx and suggest that IAP itself might be an integrin-associated calcium channel.