Insulin mitogen-activated protein kinase

Bouaboula, M., Perrachon, S., Milligan, L., Canatt, X., Rinaldi-Carmona, M., Portier, M., Barth, F., Calandra, B., Pecceu, F., Lupker, J., Maffrand, J.-P., Le Fur, G., and Casellas, P. (1997). A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor. J. Biol. Ckem. 272 22330-22339. 

Figure 11.2 Structure of the insulin receptor (a). Binding of insulin promotes autophosphorylation of the (3-subunits, where each (3-subunit phosphorylates the other (3-subunit. Phosphate groups are attached to three specific tyrosine residues (tyrosines 1158, 1162 and 1163), as indicated in (b). Activation of the (3-subunit s tyrosine kinase activity in turn results in the phosphorylation of various intracellular (protein) substrates which trigger the mitogen-activated protein kinase and/or the phosphoinositide (PI-3) kinase pathway responsible for inducing insulin s mitogenic and metabolic effects. The underlying molecular events occurring in these pathways are complex (e.g. refer to Combettes-Souverain, M. and Issad, T. 1998. Molecular basis of insulin action. Diabetes and Metabolism, 24, 477-489)...

The effects of insulin on transcription are shown on the left of the illustration. Adaptor proteins Crb-2 and SOS ( son of sevenless ) bind to the phosphorylated IRS (insulin-receptor substrate) and activate the G protein Ras (named after its gene, the oncogene ras see p.398). Ras activates the protein kinase Raf (another oncogene product). Raf sets in motion a phosphorylation cascade that leads via the kinases MEK and ERK (also known as MARK, mitogen-activated protein kinase ) to the phosphorylation of transcription factors in the nucleus. 

Carrillo, J.J. Ibares, B. Esteban-Gamboa, A. Feliu, J.E. Involvement of both phosphatidylinositol 3-kinase and p44/p42 mitogen-activated protein kinase pathways in the short-term regulation of pyruvate kinase L by insulin. Endocrinology, 142, 1057-1064 (2001)... 

The mitogen-activated protein kinase pathway (MAPK) on the right side of Figure 11.1 is also activated via the adaptor protein GRB-2 after insulin binds to its receptor. This activated kinase pathway eventually leads to the phosphorylation of... 

Denton, R.M., and J.M. Tavare. 1995. Does mitogen-activated-protein kinase have a role in insulin action The cases for and against. Eur. J. Biochem. 227 597-611. 

AUister, E. M., Borradaile, N. M., Edwards, J. Y., Huff, M. W. (2005). Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein BlOO secretion by the citms flavonoid naiingenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes. Diabetes, 54, 1676-1683. 

Lazar, D.F., Wiese, R.J., Brady, M.J., Mastick, C.C., Waters, S.B., Yamauchi, K., Pessin, J.E., Cuatrecasas, P. and Saltiel, A.R. Mitogen-activated protein kinase inhibition does not block the stimulation of glucose utilization by insulin. J. Biol. Chem., 1995, 270, 20801-20807. 

J. WijKANDER, T. R. LANDSTROM, V. MANGANIELLO, P. Belfrage, and E. Degerman, Insulin-induced phosphorylation and activation of phosphodiesterase 3B in rat adipocytes possible role of protein kinase B but not mitogen-activated protein kinase or p70 S6 kinase, Endocrinology, 1998, 139, 219-227. 

He, HJ, Kole, S, Kwon, YK, Crow, MT, and Bernier, M, Interaction of filamin a with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway, J Biol Chem, 2003. 278(29) 27096-27104. 

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