of work: A number of signaling intermediates and membrane-associated glycoproteins can regulate the insulin receptor function by interacting with different regions of this receptor. Because of the important role that intracellular reduction/oxidation potential plays in the modulation of insulin action, we postulated that the interaction between the insulin receptor and associated proteins may be affected by the reactivity of the receptor cytoplasmic thiol(s). In this study, we examined the role of various receptor domains and specific insulin receptor cysteine residues in this association. The results showed the formation of a large complex between the wild-type human insulin receptor beta-subunit and TRAP, a thiol reactive membrane-associated protein, whose identity remains to be elucidated. A series of experiments revealed that a single cysteine residue near the juxtamembrane region of the human insulin receptor is responsible for this interaction. Known signaling intermediates are not part of the receptor-TRAP complex. Hence, work is underway to identify TRAP. Also, the effects of oxidants and antioxidants on the formation and cellular distribution of the insulin receptor-TRAP heterocomplex is currently evaluated. Since TRAP is associated with the insulin receptor cytoplasmic domain both in unstimulated cells and cells treated with insulin, it may represent an accessory protein that interacts constitutively with the insulin receptor, enabling recruitment of signaling intermediates at the plasma membrane in response to insulin challenge.
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| Zhu, Min; Miura, Junnosuke; Lu, Lucy X et al. (2004) Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization. Exp Gerontol 39:1049-59 |
| Kwon, Yong-Kook; Jang, Hyeung-Jin; Kole, Sutapa et al. (2003) Role of the pleckstrin homology domain of PLCgamma1 in its interaction with the insulin receptor. J Cell Biol 163:375-84 |
| He, Hua-Jun; Kole, Sutapa; Kwon, Yong-Kook et al. (2003) Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. J Biol Chem 278:27096-104 |
