Receptors for Insulin and Growth Factors

Insulin exerts its effects by altering the state of phosphorylation of certain intracellular enzymes by a mechanism that does not involve cAMP but that requires specific binding to surface receptors with tyrosine kinase activity. Insulin exerts acute (minutes), delayed-onset (hours), and longterm (days) effects entirely by way of a single receptor. 

The insulin receptor is a transmembrane heterotetramer consisting of one pair each of two dissimilar subunits linked by disulfide bridges (Chapter 22). Both subunits 

In states of chronically elevated blood levels of insulin, there is a substantive decrease in the density of insulin receptors in insulin-dependent cells due to a decrease in the synthesis of insulin receptors. This phenomenon, which is referred to as downregulation, represents a means by which a cell autoregulates its receptivity to the hormone, and is also detected by other hormones such as the catecholamines, endorphins, and GnRH. The precise mechanisms involved in downregulation are not known. 

The insulin receptor is expressed in most cells and tissues examined to date, including the non-insulin-dependent tissues such as brain, kidney, and blood cells (both red and white). Although no specific cellular response to insulin has been described in these tissues, it is conceivable that insulin regulates one or more intracellular 

Mechanism of prolactin receptor activation. Activation of prolactin receptor consists of ligand-induced sequential receptor homodimerization driven by the two binding sites of prolactin. In the intracellular domain of the homodimer of the ligand-receptor complex, a tyrosine kinase [known as Janus kinase 2 (Jak-2)] is activated. Jak-2 kinase causes autophosphorylation and phosphorylation of the receptor. [Reproduced with permi,ssion from M. E. Freeman, 

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In contrast to the receptors for insulin and growth factors (see p. 388), the cytokine receptors (with a few exceptions) have no tyrosine kinase activity. After binding of cytokine (1), they associate with one another to form homodimers, join together with other signal transduction proteins (STPs) to form dimers, or promote dimerization of other... 

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