Insulin action cascade

Figure 25-14 Mechanism of insulin action. Binding of insulin to the extracellular a-subunit of the insulin receptor induces autophosphorylation of the -subunit of the receptor and phosphorylation of selected intracellular proteins, such as She and the IRS family,These latter phosphoproteins interact with other targets, thereby activating phosphorylation cascades, which result in glucose uptake (in adipose tissue and skeletal muscle), glucose metabolism, synthesis (of glycogen, iipid, and proteins), enhanced gene expression, cell growth, and differentiation, p, protein phosphorylation aPKC, atypical protein kinase C, See text for details.

See also Pancreas Anatomy, Glycogen Regulatory Cascade (from Chapter 13), Action of Insulin, Action of Epinephrine, Response to Starvation... 

Insulin binds to specific, high-affinity receptors in the cell membrane of most tissues, including liver, muscle, and adipose. This is the first step in a cascade of reactions ultimately leading to a diverse array of biologic actions. 

Some of the components participating in the insulin-regulated kinase cascade, play also a role in signalling by other growth factors and cytokines. A common reservoir of tools, shared by other growth factors, strengthens the argument that the action of insulin on... 

P. Cohen. Dissection of the protein phosphorylation cascades involved in insulin and growth factor action. Biochem Soc Trans, 21, 555-567, 1993. 

At the cellular and molecular level, the binding of insulin to a specific membrane spanning receptor initiates a signal transduction cascade which ultimately produces the biological actions of the hormone. The insulin receptor is a tetrameric protein comprised of two a subunits that bind to insulin and two j3 subunits that are linked by disulfide bonds (55,56), and belongs to a subfamily of receptor typrosine kinases which also includes the insulin-like growth factor I (IGF-I) receptor. The a subunits are extracellularly located, while (S subunits span the membrane and have... 

Our consideration of the signal-transduction cascades initiated by epinephrine and insulin included examples of how components of signal-transduction pathways are poised for action, ready to be activated by minor modifications. For example, G-protein a subunits require only the binding of GTP in exchange for GDP to transmit a signal. This exchange reaction is thermodynamically favorable, but it is quite slow in the absence of an appropriate activated 7TM receptor. Similarly, the tyrosine kinase domains of the dimeric insulin receptor are ready for phosphorylation and activation but require the presence of insulin bound between two a subunits to draw the activation loop of one tyrosine kinase into the active site of a partner tyrosine kinase to initiate this process. 

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