Insulin receptor isoforms

The catalytic pi 10 subunit has four isoforms, all of which contain a kinase domain and a Ras interaction site. In addition, the a, (3, and y isoforms possess an interaction site for the p85 subunit. The class I enzymes can be further subdivided class IA enzymes interact through their SH2 domains with phosphotyrosines present on either protein tyrosine kinases or to docking proteins such as insulin-receptor substrates (IRSs GAB-1) or linkers for activation of T cells (LATs in the case of T cells). 

Kerouz, N.J. Horsch, D. Pons, S. Kahn, C.R. Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ ob) mouse. J. Clin. Invest., 100, 3164-3172 (1997)... 

The two common isoforms of the insulin receptor (Fig. 11-11) arise because a 36-nucleotide (12-amino acid) exon is spliced out of the mRNA for the shorter protein. Isoenzymes of aldolase34 and of many other proteins are formed in a similar manner. Frame-shifting during protein synthesis (Chapter 29) and also post-translational alterations may give rise to additional modified forms. They are often synthesized in relatively small amounts but may be essential to the life of the cell. In addition, genetic variants of almost any protein will be found in any population. These often differ in sequence by a single amino acid. 

In this context interest is focused on PKC, which plays a key role in mediating signals generated by hormones, growth factors and neurotransmitters (Nishizuka, 1988). Several isoforms of PKC have been described which show distinct sensitivity to Ca2+ and phospholipid-degradation products (Nishizuka, 1988). Their specific function, however, is not defined. It has been demonstrated previously that phorbol esters are potent activators of PKC and induce inhibition of the catalytic domain of the insulin receptor probably via serine phosphorylation of the insulin receptor )8-subunit (Muller et al., 1991). 

Fernandez, R. Tabarini, D. Azpiazu, N. Frasch, M. Schlessinger, J. The Drosophila insulin receptor homolog a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. EMBO J., 14, 3373-3384 (1995)... 

Sugimoto, K, Murakawa, Y, Zhang, W, Xu, G, and Sima, AA, Insulin receptor in rat peripheral nerve its localization and alternatively spliced isoforms. Diabetes Metab Res Rev, 2000. 16(5) 354-363. 

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