ABSTRACT

Receptor tyrosine kinases (RTKs) are cell surface receptors that play an essential role in signal transduction from extracellular stimuli (see also Chapter 12). Tyrosine phosphorylation is a post-translational modication of proteins catalyzed by enzymes that transfer phosphoryl to tyrosine residues in protein substrates, using ATP as a phosphate donor. These enzymes are protein tyrosine kinases (TK), of which there are 58 RTKs and 32 nonreceptor types in the human genome. RTKs transduce signals of polypeptide and protein hormones, and growth factors which lead to regulation of critical cellular functions. Cytokine receptors are related to RTKs as their signaling is also propagated via tyrosine phosphorylation of intracellular proteins. Unlike RTKs, the cytokine receptors lack the intrinsic TK domain. Instead, the Janus kinases (JAK) which are noncovalently associated

22.1 Introduction .......................................................................................................................... 387 22.2 RTK Family .......................................................................................................................... 388

22.2.1 Cytokine Receptors .................................................................................................. 389 22.2.2 RTKs as Drug Targets .............................................................................................. 389 22.2.3 Cytokine Receptors as Drug Targets ........................................................................390