Phosphorylation cascades receptor kinases

Store it while it s here. Insulin binds to a specific receptor on the cell surface and exerts its metabolic effect by a signaling pathway that involves a receptor tyrosine kinase phosphorylation cascade. Note that insulin stimulates storage processes and at the same time inhibits degradative pathways. 

The effects of insulin on transcription are shown on the left of the illustration. Adaptor proteins Crb-2 and SOS ( son of sevenless ) bind to the phosphorylated IRS (insulin-receptor substrate) and activate the G protein Ras (named after its gene, the oncogene ras see p.398). Ras activates the protein kinase Raf (another oncogene product). Raf sets in motion a phosphorylation cascade that leads via the kinases MEK and ERK (also known as MARK, mitogen-activated protein kinase ) to the phosphorylation of transcription factors in the nucleus. 

Althou the role of the MAP kinase phosphorylation cascade in the control of cell growth and cellular proliferation is undisputed, other pathways and pathway ramifications contribute to that control. This requires communication between signal transduction pathways. MAP kinase also seems to play a part in pathway interconnections, for example in connecting signals from G-protein-coupled receptors with signals from growth-factor-activated receptors (discussed in Chapter 5). 

Receptors with intrinsic or acquired kinase activity generate the input signal. The response of receptor kinases to activation by the ligand is slow and so is the cellular response. Phosphorylation of receptors initiates phosphorylation cascades and cytosolic... 

AUTOACTIVATION OF THE RECEPTOR KINASE BY TYROSINE PHOSPHORYLATION THE AUTOPHOSPHORYLATION 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.

Figure 28-2 Signal transduction by cell-surface receptors that are coupled to G-proteins.Two seven-transmembrane domains, coupled to different G-proteins (Gs, and G,) are shown. Activation of Gs leads to stimulation of the effector enzyme adenylate cyclase and the production of a cAMP second messenger, causing the activation of protein kinase A (PKA) and the initiation of potential phosphorylation cascades. Activation of G leads to stimulation of the effector enzyme phospholipase C p and the production of IP3 and diacylglycerol (DAG) second messengers, one effect of which is to activate protein kinase C (PKC) and Initiate a potential phosphorylation cascade. (From Conn PM.Mefmed S, eds.Textbook of endocrinolog/.Towanta Nj Humana Press 1997.)...

---