GROWTH-HORMONE INDUCES TYROSINE PHOSPHORYLATION OF ANNEXIN-I IN RAT OSTEOSARCOMA CELLS

GH induces phosphorylation of a number of cellular proteins, of which several have now been identified, such as mitogen-activated protein ki nase, insulin receptor substrate-1, and members of the JAK kinase and STAT families of proteins. However, other phosphorylated proteins rema in unidentified. Growth factors and cytokines, including epidermal fac tor, insulin, pp60(v-scr), and angiotensin II, induce a rapid phosphor ylation of annexin I, a 35-kDa member of the annexin family Ca2+ and p hospholipid-binding proteins. The osteoblast-like rat osteosarcoma cel l-line UMR-106.01, in which GH acts as a mitogen via a high affinity G H receptor, was used a model for GH-induced protein phosphorylation. I t is demonstrated by immunoblotting and immunoprecipitation techniques that GH induces the phosphorylation of annexin I on tyrosine residues . This phosphorylation is dose and time dependent. Induction of annexi n I phosphorylation is delayed compared with that of JAK2. These resul ts identify annexin I as a protein that becomes tyrosine phosphorylate d under the influence of GH and show that phosphorylation of annexin I is a general phenomenon that follows activation of a cell by hormones or cytokines.