What Is the Function of an Insulin Receptor
The hormone insulin acts on liver and muscle cells to initiate a series of reactions in which glucose is removed from the blood stream and polymerized as glycogen. In addition to its effect on glucose uptake and metabolism, insulin is also a powerful stimulant of lipid synthesis, protein synthesis, as well as growth and proliferation. The mechanism by which insulin stimulates these various responses eluded investigators for many years. But during the past decade great strides have been made in elucidating the mechanism by which insulin interacts with the outer surface of the target cells and signals its presence to various effectors within the cell interior. Insulin acts by means of signaling pathway that is different in many respects from that used by glucagon and epinephrine.
The insulin receptor is more than just a protein that binds a ligand; it is also an enzyme – a protein tyrosine kinase, an enzyme that adds phosphate groups to specific tyrosine residues of other proteins. Tyrosine kinases compose a superfamily distinct from the serine and threonine kinases that operate in the reaction cascade. Although, a small number of tyrosine kinases have dual specificity and are also able to phosphorylate serine and threonine residues. Tyrosine kinases are involved primarily in the control of cell growth and differentiation, rather than control of intermediary metabolism. Since the insulin receptor has this enzymatic activity, it is referred to as a receptor tyrosine kinase(or RTK). There are number of RTK and each RTK monomer traverses the membrane only once.
Function of RTK:
The insulin receptor is tetrameric protein composed of two alpha and two beta polypeptide chains. The alpha chain resides on the extracellular surface of the membrane and contains insulin-binding sites, whereas beta-chains span the membrane and transmit the signal across the membrane to its inner surface. In the absence o f bound insulin, the tyrosine kinase function of the receptor is inactive. Binding of insulin changes the conformation of the receptor , activating its tyrosine kinase, which then adds phosphates to 1) specific tyrosine residues of the other beta subunit of the complex, a reaction termed autophosphorylation, and 2) a dozen or more strategically located tyrosine residues of at least two protein substrates, called insulin receptor substrates (IRSs). Phosphorylated IRSs appear to have only one function, which is to bind and activate a variety of “downstream” effectors.
RTKs do not phosphorylate every tyrosine in a substrate protein; they phosphorylate only those that are present within certain amino acid sequences that are referred to as “phosphotyrosine motifs”. A recent study have revealed that a variety of proteins involved in cell signaling contain domains, called SH2 domains, with high affinity binding sites for “phosphotyrosine motifs”.
The hormone insulin acts on liver and muscle cells to initiate a series of reactions in which glucose is removed from the blood stream and polymerized as glycogen