Annexin I as a potential inhibitor of insulin receptor protein tyrosine kinase.
Insulin receptor (IR) purified from human placenta by wheat germ agglutinin affinity chromatography was incubated in the presence of insulin, [gamma-32P]ATP and annexin I. In parallel to its own tyrosine phosphorylation, annexin I promoted a dose-dependent inhibition of IR autophosphorylation (IC50 0.5 microM). This effect was specific for insulin-stimulated tyrosine kinase activity and required the N-terminal end of the protein containing the phosphorylatable Tyr21 residue. A pentadecapeptide encompassing residues 16-30 of human annexin I displayed a similar activity, but at higher concentrations. These data underscore a specific interaction of IR with annexin I, which should be considered as a potential physiological regulator of the effects of insulin on its target tissues.
Melki
V
V
INSERM Unité 326, Hôpital Purpan, Toulouse, France.
Hullin
F
F
Mazarguil
H
H
Fauvel
J
J
Ragab-Thomas
J M
JM
Chap
H
H
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D010920:Placenta / Q000737:chemistry; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D017305:Annexin A1; D007328:Insulin; D010446:Peptide Fragments; D000255:Adenosine Triphosphate; D011972:Receptor, Insulin