Insulin receptor /3-subunit functional domains

Insulin Receptor. Figure 1 Structure and function of the insulin receptor. Binding of insulin to the a-subunits (yellow) leads to activation of the intracellular tyrosine kinase ((3-subunit) by autophosphorylation. The insulin receptor substrates (IRS) bind via a phospho-tyrosine binding domain to phosphorylated tyrosine residues in the juxtamembrane domain of the (3-subunit. The receptor tyrosine kinase then phosphorylates specific tyrosine motifs (YMxM) within the IRS. These tyrosine phosphorylated motifs serve as docking sites for some adaptor proteins with SRC homology 2 (SH2) domains like the regulatory subunit of PI 3-kinase. 

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). 

The cytoplasmic domain of the P-subunit displays three distinct sub-domains (a) the juxtam-embrane domain , implicated in recognition/binding of intracellular substrate molecules (b) the tyrosine kinase domain, which (upon receptor activation) displays tyrosine kinase activity (c) the C-terminal domain, whose exact function is less clear, although site-directed mutagenesis studies implicate it promoting insulin s mitogenic effects. 

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