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.
Schwartz
M A
MA
Committee on Vascular Biology, Scripps Research Institute, La Jolla, California 92037.
Brown
E J
EJ
Fazeli
B
B
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D051928:CD47 Antigen; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008970:Molecular Weight; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D005353:Fibronectins; D016023:Integrins; D006632:Histamine; D002118:Calcium