Aagaatggacccagttcttgtacatatggatattctttga Rmdpvlvhmdi L

FIGURE 3-11 Seven-transmembrane-spanning model of the TRH receptor showing the situation of the divergent carboxyl-terminal sequence of TRH-R(387). The membrane orientation of the receptor is drawn on the basis of the proposed topography of homologous receptors. The arrangement of the hydrophilic sequences is arbitrary. Putative sizes for phosphorylation by protein kinase C (crosses), protein kinase A (open triangle), and casein kinase II (filled triangles) are indicated in the carboxyl-terminal domain. The nucleotide and amino acid (in single-letter code) sequences of the deleted sequence and its boundaries are shown at the bottom. Numbers indicate the amino acid position in the open reading frame. Reproduced with permission from de la Pena, P., Delgado, L. M., del Camino, D., and Barros, F. (1992). Two isoforms of the thyrotropin-releasing hormone receptor generated by alternative splicing have indistinguishable functional properties. /. Biol. Chem. 267, 25703-25708.

which seems to be lacking in the human GnRH receptor. Possibly other receptors for other releasing hormones may fall into this class of seven-membrane-spanning domain receptors.

E. Molecular Mechanisms of Action

Releasing hormones act at cognate plasma membrane receptor levels either to cause an increase in cyclic AMP or to stimulate the phosphatidylinositol cycle, leading to the stimulation of protein kinase C and an increase in cytoplasmic calcium ion concentration. These actions are summarized in Table 3-4.

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