Annexin II is a novel player in insulin signal transduction. Possible association between annexin II phosphorylation and insulin receptor internalization.
Annexin II is a Ca2+-, phospholipid-, and actin- binding protein that was implicated in the regulation of vesicular traffic and endosome fusion. It is a known substrate for protein kinases including the platelet-derived growth factor receptor, src protein-tyrosine kinase, and protein kinase C. In the present study we investigated the possible involvement of annexin II in insulin signal transduction. Phosphorylation of annexin II in response to insulin treatment of intact Chinese hamster ovary (CHO)-T cells was detected by 5 min and reached maximal levels after a 2-3-h incubation with the hormone. However, unlike other receptor substrates, annexin II failed to undergo insulin-induced Tyr phosphorylation under conditions where receptor internalization was inhibited. This was evident in CHO cells, overexpressing the insulin receptor, in which internalization was inhibited either by tyrosine kinase inhibitors or by lowering the temperature to 4 degrees C, and in CHO cells overexpressing various insulin receptor mutants in which normal internalization was impaired. Hence, Tyr phosphorylation of annexin II could be part of the internalization and sorting mechanism of the insulin receptor.
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel. Lizick@weizmann.weizmann.ac.il
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Biener
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Feinstein
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Mayak
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Kaburagi
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Kadowaki
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Zick
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D016466:CHO Cells; D002396:Catechols / Q000494:pharmacology; D006224:Cricetinae; D004705:Endocytosis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins; D000077191:Wortmannin
D000730:Androstadienes; D017306:Annexin A2; D002396:Catechols; D004791:Enzyme Inhibitors; D007328:Insulin; D009570:Nitriles; D020032:Tyrphostins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; C060641:tyrphostin A23; D011188:Potassium; D000077191:Wortmannin