The annexins are a family of proteins that bind acidic phospholipids in the presence of Ca2+. The interaction of these proteins with biological membranes has led to the suggestion that these proteins may play a role in membrane trafficking events such as exocytosis, endocytosis and cell-cell adhesion. One member of the annexin family, annexin II, has been shown to exist as a monomer, heterodimer or heterotetramer. The ability of annexin II tetramer to bridge secretory granules to plasma membrane has suggested that this protein may play a role in Ca(2+)-dependent exocytosis. Annexin II tetramer has also been demonstrated on the extracellular face of some metastatic cells where it mediates the binding of certain metastatic cells to normal cells. Annexin II tetramer is a major cellular substrate of protein kinase C and pp60src. Phosphorylation of annexin II tetramer is a negative modulator of protein function.