Biochemistry and Cellular Distribution of the Growth Hormone Receptor
Growth hormone (GH) is the major hormone regulating postnatal growth and an important regulator of metabolism. Because these actions are the result of interactions of GH with its receptor, not surprisingly the receptor has been the focus of much attention. When we reported the cloning of the human and rabbit GH receptors (Leung et al. 1987), the GH receptor was structurally unique, and its sequence gave no mechanistic clues. Subsequently, when Boutin et al. (1988) and ourselves (Waters et al. 1988, 1990) reported a 30% sequence homology between the GH receptor and the prolactin receptor, it became apparent that these two receptors constituted a new class of transmembrane signalling molecules. With the subsequent cloning of a number of hematopoietic receptors, it became clear that the GH receptor is structurally related to a major class of cytokine receptors, involved in regulating cell committment, proliferation and differentiation (Bazan 1989, 1990 Cosman et al. 1990). These receptors are single transmembrane proteins with significant (approximately 20%) homology in their extracellular region, and comprise the erythropoietin, granulocyte macrophage colony stimulating factor, interleukins 2-7, tumour necrosis factor-α and LIF receptors in addition to GH and prolactin receptors. These receptors also have two short homologous domains in the cytoplasmic region, which may be concerned with mitogenic triggering (Sakamaki et al. 1992). The cytokines themselves, although dissimilar in sequence, were predicted to have a common secondary structure of a four antiparallel α helix bundle (Bazan 1990) analagous to that of GH (Abdel-Meguid et al. 1987), a proposal thus far verified with crystallographic structures (Diederichs et al. 1991 Wlodaver et al. 1992).
KeywordsGrowth Hormone Human Growth Hormone Growth Hormone Receptor Prolactin Receptor Bovine Growth Hormone
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