PARTICIPATION OF ANNEXINS IN PROTEIN-PHOSPHORYLATION

Simultaneous discovery of members of the annexin family of calcium and phospholipid binding proteins by several groups is intimately linked to the possibility that these proteins may be controlled by phosphoryl ation. Indeed, annexin I and annexin II have bees identified as major substrates for the tyrosine kinase activity associated with epidermal growth factor receptor (EGF-R) and for the retrovirus encoded protein tyrosine kinase pp60(r-src) Both annexins are also in vitro and/or in situ substrates for platelet derived growth factor (PDGF), insulin and hepatocyte growth factor/scatter factor (HGF/SF) receptor tyrosine ki nases. In addition, to serve as substrates for tyrosine protein kinase s some annexins are cellular targets for serine/threonine protein kina ses such as protein kinase C (PKC) and cAMP-dependent protein kinase A (PKA). Although the role of annexin phosphorylation has not been stud ied in detail, it is thought to influence their vesicle aggregation an d phospholipid binding properties. Some annexins are also potent inhib itors of various serine/threonine and tyrosine kinases. The physiologi cal functions of the annexins have still not been clearly defined. The refore the identification of the ability of these proteins to undergo phosphorylation may be helpful in assigning them a precise biological role.