Growth Hormone Receptor (GHR)

Growth Hormone Receptor (GHR) is a 620-638 amino acid transmembrane protein belonging to the class I cytokine receptor family. It exists as a full-length membrane-bound receptor and a soluble growth hormone binding protein (GHBP). The membrane-bound form has an extracellular domain, a single transmembrane domain, and a cytoplasmic intracellular domain. Unlike other class I cytokine receptors, GHR lacks the WSXWS motif. GHR activation involves one growth hormone molecule binding to two GHR molecules, inducing a conformational change that activates associated JAK2 kinases. This initiates primary signaling through the JAK-STAT pathway (especially STAT5), as well as activating Src family kinases and other pathways (SHC, IRS, MAPK, PKC, PLA2, PI3K). GHR signaling is negatively regulated by SOCS proteins and phosphatases (SHP1, SHP2). GHR plays crucial roles in regulating normal growth and development, metabolism, and various physiological processes in multiple organ systems, and is involved in aging and cancer development. Mutations in GHR are associated with Laron syndrome (growth hormone insensitivity syndrome). GHR antagonists such as pegvisomant are used in the treatment of acromegaly. GHR is also considered a promising drug target in prostate, breast, pancreatic, and ovarian cancers.

Other names

GH receptorGHBPGrowth Hormone Binding Protein

Growth hormone receptor antagonism