Protein receptor defects

Beckwith and his colleagues isolated a large family of mutants that were permanently catabolite-repressed. These mutants fell into two categories Those that could be pheno-typically corrected by growing in the presence of cAMP and those that could not. The first class of mutants were believed to be defective in the synthesis of cAMP, and the latter class were presumed to be defective in the protein receptor for cAMP. Cell-free extracts were prepared from... 

Subsequent work revealed that the "satiety factor" is a protein called Jeptinand that its target is a receptor in the hypothalamus. Attention to the cause of human obesity has focused on changes in the structure of the Jeptin receptor, defects in the mechanism of transport of serum leptin to the brain (Schwartz ef aL, 1996 Caro et al., 1996), and on mutations that affect the signaling proteins that respond to the leptin receptor... 

An increasing number of diseases are known to be linked to defects in receptor stmcture, function, or coupling. The defects may He at several locations in the stmcture of the receptor, which may alter its abiHty either to bind dmgs, to be inserted into the membrane, or to couple to effectors (including G-proteins) in the coupling protein or in the presence of autoantibodies, which can proceed to activate, block, or lyse the receptors and its components (96—99). 

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

We have gained considerable insight into the therapeutic potential of this protein through the use of TGF-(3 antagonists and transgenic mice with defective TGF-(3 signaling and we have evaluated the potential toxicity of TGF-(3 modulation and its overall efficacy in treating cancer. FC Soluble Type II Receptor... 

The disorders listed are discussed further in other chapters. The table lists examples of mutations affecting receptors, a transporter, an ion channel, an enzyme, and a structural protein. Examples of altered or defective glycosylation of glycoproteins are also presented. Most of the conditions listed affect the plasma membrane. 

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