Molecular recognition events involved in the activation of the growth hormone receptor by growth hormone

Abstract

Binding of growth hormone (GH) to its receptor (GHR) is a well-studied example of molecular recognition between a cytokine and its receptor. Extensive mutagenesis studies and several crystal structures have defined the key interactive amino acid residues that are involved in binding and subsequent receptor dimerization. This review encompasses each of the three molecular recognition events involved in GHR activation, namely binding of GH to its two receptors and the interactions that occur between these receptors. Particular attention is given to species and ligand specificity of hormone binding and to the molecular recognition events involved in receptor activation, including the possibility that a conformational change in the receptor is required.

Transcriptome Analysis Reveals Differences in Gene Expression in the Muscle of the Brown-Marbled Grouper (Epinephelus fuscoguttatus) with Different Growth Rates

“…ghr (the growth hormone receptor) is a cell membrane receptor that specifically binds to growth hormone (GH). Upon binding, ghr initiates a phosphorylation cascade that regulates signaling and gene expression, ultimately regulating various physiological functions such as growth, metabolism, appetite, reproduction, and social behavior [33,34]. Based on a study of Rohu (Labeo rohita), it was found that several molecules have agonistic effects on the growth hormone receptor protein, and these molecules can be utilized to enhance ray-finned fish growth [35].…”

Transcriptome Analysis Reveals the Difference of Gene Expression in Muscle of the Brown-Marbled Grouper (Epinephelus fuscoguttatus) With Different Growth Rates

“…Upon binding, ghr initiates a phosphorylation cascade that regulates signaling and gene expression, ultimately regulating various physiological functions such as growth, metabolism, appetite, reproduction, and social behavior. (Behncken and Waters, 1999;Zhu, et al, 2001). Based on the study of Rohu (Labeo rohita), it was found that several molecules have agonistic effects on growth hormone receptor protein, and these molecules can be utilized to enhance fish growth (Dhandare, et al, 2020).…”

Clinical and biochemical consequences of an intragenic growth hormone receptor (GHR) deletion in a large Chinese pedigree

“…Truncated proteins as a result of exon 7 PTC mutations – if expressed – can be expected to be secreted directly into the circulation as well, but in the affected patients, GHBP serum concentrations were extremely low or undetectable. Failure to detect GHBP in these patients is possibly assay‐related; however, major determinants involved in GH binding are probably disturbed . In contrast, GHBP‐like proteins generated due to exon 8 skipping have been demonstrated to retain their GH‐binding properties .…”

“…Failure to detect GHBP in these patients is possibly assayrelated; however, major determinants involved in GH binding are probably disturbed. 25,26 In contrast, GHBP-like proteins generated due to exon 8 skipping have been demonstrated to retain their GH-binding properties. 4,8,9 Nonetheless, not even an extreme elevation of serum GHBP-like peptides interferes with GH action in the presence of at least one functional GH receptor copy, as heterozygous carriers of exon 8 skipping mutations are not GH insensitive [ 8 and this study].…”