Growth hormone receptors

Dimerization of the growth hormone receptor is a sequential process... 

The prolactin receptor, PER, which regulates milk production in mammals, belongs to the same receptor class as the growth hormone receptor. In addition to binding the hormone prolactin, PER also binds and is activated by growth hormone. The extracellular domain of PER forms a very stable 1 1 complex with growth hormone in solution this complex has been crystallized and its structure determined (Figure 13.21). We shall compare this structure with the 1 2 complex of the same hormone with GHR. 

Figure 13.22 Hormone-receptor interactions involving the domain-domain linker region in the receptor, (a) Interactions between the growth hormone (red) and the growth hormone receptor (blue) linker region. Glu 127 of the receptor forms a salt bridge to Arg 167 in the hormone, (b) The same interaction area in the growth hormone (red)-prolactin receptor (green) complex. The displacement of the linker region due to differences in the domain orientations have brought Asp 124 in the prolactin receptor into contact with Arg 167 of the hormone. (Adapted from W. Somers et al.. Nature 372 478-481, 1994.)...

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

Cunninghum BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 1991 254 821-825. 

FIGURE 4.3 Growth hormone receptor. Monomeric GH associates with two receptor monomers. Activated JAK2 kinases /ram-phosphorylatc JAK2 and GH receptors, and STAT transcription factors are phosphorylated by JAK2. 

Pearce, K.H., Jr., M.H. Ultsch, R.F. Kelley, A.M. de Vos, and J.A. Wells. 1996. Structural and mutational analysis of affinity-inert contact residues at the growth hormone-receptor interface. Biochemistry 35 10300-10307. 

Covers, R., T. ten Broeke, P. van Kerkhof, A. L. Schwartz, and G. J. Strous. Identification of a novel ubiquitin conjugation motif required for ligand-induced internalization of the growth hormone receptor. Embo J. 18 28-36.1999. 

Ubiquitin System-Dependent Regulation of Growth Hormone Receptor Signal Transduction and Effects of Oxidative Stress... 

Regulation of Growth Hormone Receptor Signal Transduction... 

Although ubiquitin-conjugation of receptors in mammalian cells has been observed, the function of this modification seems less clear. In the case of the growth hormone receptor (GH-receptor) and the epithelial Na-t- channel (ENaC), it seems likely that ubiquitin-conjugation triggers their endocytosis. 

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