Key Concepts of Section 16.3

• Receptor tyrosine kinases, which bind to peptides and signaling proteins such as growth factors and insulin, may exist as preformed dimers or dimerize during binding to ligands. Ligand binding triggers formation of functional dimeric receptors, a necessary step in activation of the receptor-associated kinase, and different receptors accomplish this function in different ways (see Figures 16-14, 16-15, and 16-16).

• Activation of many RTKs leads to phosphorylation of the activation loop in the protein tyrosine kinase that is an intrinsic part of the cytoplasmic domain, enhancing its catalytic activity (see Figure 16-14). The activated kinase then phosphorylates tyrosine residues in the receptor cytosolic domain and in other protein substrates.

• Humans express many RTKs, four of which (HER1–HER4) define the epidermal growth factor receptor family that mediates signaling from different members of the epidermal growth factor family of signaling molecules (see Figure 16-17). One of these receptors, HER2, does not bind ligand; it forms active heterodimers with ligand-bound monomers of the other three HER proteins. Overexpression of HER2 is implicated in many breast cancers.

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  Endocytosis of receptor-hormone complexes and their degradation in lysosomes is a principal way of reducing the number of receptor tyrosine kinases and cytokine receptors on the cell surface and thus decreasing the sensitivity of cells to many peptide hormones.