Annexin II Is a Novel Player in Insulin Signal Transduction

Abstract

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.

Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B

“…In addition, blocking IR internalization led to inhibition of SHC phosphorylation and activation, whereas no effect was detected on IR autophosphorylation or IRS1 and AKT kinase phosphorylation and activation (Biener et al, 1996;Ceresa et al, 1998;Hamer et al, 2002), suggesting that these signaling elements can be fully activated by IRs at the surface. That is, the metabolic response of insulin appears to be fully activated from IRs on the cell surface.…”

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

“…Thus, Anx2 is associated with the regulation of DNA synthesis, and probably also with the cell cycle (Chiang et al, 1993) and cellular proliferation (Kumble et al, 1992b). Other functions include regulation of membrane trafficking such as exocytosis (Liu et al, 1996;Konig et al, 1998) and actin filament bundling (Jones et al, 1992), immunosuppression in RCC (Aarli et al, 1997) and insulin-induced signal transduction (Biener et al, 1996). However, few studies have focused on the role of Anx2 in the pathological conditions induced by ROS.…”

Regulation of Complex Formation of POB1/Epsin/Adaptor Protein Complex 2 by Mitotic Phosphorylation

“…Insulin Binding and Internalization Assay-The activities of the binding and the internalization of insulin in CHO-IR cells were determined as described previously (19,27,34,35). Briefly, confluent wild type CHO-IR cells and CHO-IR cells expressing POB1, hEpsin or their mutants (35-mm-diameter dishes) were incubated with 100 pM [ 125 I]insulin (4 -5 ϫ 10 3 cpm/pmol) for 5 h at 4°C.…”