ANNEXIN-I AS A POTENTIAL INHIBITOR OF INSULIN-RECEPTOR PROTEIN-TYROSINE KINASE

Insulin receptor (IR) purified from human placenta by wheat germ agglu tinin affinity chromatography was incubated in the presence of insulin , [gamma-P-32]ATP and annexin I. In parallel to its own tyrosine phosp horylation, annexin I promoted a dose-dependent inhibition of IR autop hosphorylation (IC50 0.5 mu M). This effect was specific for insulin-s timulated tyrosine kinase activity and required the N-terminal end of the protein containing the phosphorylatable Tyr21 residue. A pentadeca peptide encompassing residues 16-30 of human annexin I displayed a sim ilar activity, but at higher concentrations. These data underscore a s pecific interaction of IR with annexin I, which should be considered a s a potential physiological regulator of the effects of insulin on its target tissues. (C) 1994 Academic Press, Inc.