Receptor tyrosine kinases signaling trigger

The second example of cell-signaling process that involves protein phosphorylation is receptor tyrosine kinase signaling (Fig. 10) (42). Receptor tyrosine kinases are transmembrane proteins with an extracellular ligand-binding domain and an intracellular tyrosine kinase domain. Ligand binding to the extracellular domain triggers receptor dimerization and/or activation, so that the intracellular catalytic domains from two receptor protein molecules can phosphorylate each other at the... 

Signaling pathways starting from receptor tyrosine kinases trigger stimulation of protein kinase C by activating phosphohpase Cy. An activating signal may also be despatched in the direction of protein kinase C - via activation of phospholipase CP -from G-protein-coupled membrane receptors (see Fig. 6.4). 

We turn now to a second important class of cell-surface receptors, the cytokine receptors, whose cytosolic domains are closely associated with a member of a family of cytosolic protein tyrosine kinases, the JAK kinases. A third class of receptors, the receptor tyrosine kinases (RTKs), contain intrinsic protein tyrosine kinase activity in their cytosolic domains. The mechanisms by which cytokine receptors and receptor tyrosine kinases become activated by ligands are very similar, and there is considerable overlap in the intracellular signal-transduction pathways triggered by activation of receptors in both classes. In this section, we first describe some similarities in signaling from these two receptor classes. We then discuss the JAK-STAT pathway, which is initiated mainly by activation of cytokine receptors. 

Two receptor classes, cytokine receptors and receptor tyrosine kinases, transduce signals via their associated or intrinsic protein tyrosine kinases. Ligand binding triggers formation of functional dimeric receptors and phosphorylation of the activation lip in the kinases, enhancing their catalytic activity (see Figure 14-5). 

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