Down-Modulation of Receptor Signaling
■ 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, thus decreasing the sensitivity of cells to many peptide hormones.
■ Bone resorption is triggered by binding of RANKL on osteoblasts to its receptor, RANK, on osteoclasts. RANKL/RANK signaling promotes tight adhesion of os-teoclasts to bone and secretion of a bone-dissolving mixture of HCl and proteases by osteoclasts (see Figure 14-31).
■ Osteoprotegerin, a decoy receptor for RANKL, inhibits osteoclast activation and bone resorption.
■ The extracellular domains of many cell-surface receptors can be produced by recombinant DNA techniques and have potential as therapeutic decoy receptors. Already in use is such a decoy receptor for TNF-a, which binds excess TNF-a associated with rheumatoid arthritis and other inflammatory diseases.
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