Key Concepts of Section 16.2

• Two broad classes of receptors activate tyrosine kinases: (1) receptor tyrosine kinases (RTKs), in which the kinase is an intrinsic part of the receptor, and (2) cytokine receptors, in which the kinase is bound tightly to the cytosolic domain of the receptor. Signaling from receptor tyrosine kinases and from cytokine receptors activates similar downstream signaling pathways (see Figure 16-6).

• Cytokines play numerous roles in development. Erythropoietin, a cytokine secreted by kidney cells, promotes proliferation and differentiation of erythroid progenitor cells in the bone marrow (see Figure 16-7) to increase the number of mature red cells in the blood.

• Cytokines such as GH, prolactin, Epo, and G-CSF have very similar tertiary structures, as do their receptors. These and related cytokines form a 1 cytokine:2 receptor complex on the cell surface (see Figures 16-8 and 16-9).

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• The cytosolic domains of cytokine receptors are tightly bound to a JAK protein tyrosine kinase, which becomes activated after cytokine binding and receptor dimerization and phosphorylates tyrosine residues in the receptor (see Figure 16-10).

• In both RTKs and cytokine receptors, short amino acid sequences containing a phosphotyrosine residue are bound by signal-transducing proteins with conserved SH2 domains. The sequence of amino acids surrounding the phosphorylated tyrosine determines which SH2 domain will bind to it (see Figure 16-11). Such protein-protein interactions are important in many signaling pathways (see Figure 16-12).

• The JAK/STAT pathway operates downstream from all cytokine receptors and some RTKs. STAT monomers bound to phosphotyrosines on receptors are phosphorylated by receptor-associated JAKs, then dimerize and move to the nucleus, where they activate transcription (see Figure 16-12).

• Signaling from cytokine receptors is terminated by the phosphotyrosine phosphatase SHP1 and several SOCS proteins (see Figure 16-13).