GHR

This gene encodes a protein that is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well-characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature. Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized. In humans and rabbits, but not rodents, growth hormone binding protein (GHBP) is generated by proteolytic cleavage of the extracellular ligand-binding domain from the mature growth hormone receptor protein. The precise location of this cleavage site has not been determined for the human protein

growth hormone receptor

Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).

The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.

Activation of Janus kinase activity Source: Ensembl
Cartilage development involved in endochondral bone morphogenesis Source: Ensembl
Cellular response to hormone stimulus Source: BHF-UCL
Cellular response to insulin stimulus Source: Ensembl
Cytokine-mediated signaling pathway Source: GO_Central
Endocytosis Source: UniProtKB-KW
Growth hormone receptor signaling pathway Source: BHF-UCL
Hormone-mediated signaling pathway Source: Ensembl
Hormone metabolic process Source: BHF-UCL
Insulin-like growth factor receptor signaling pathway Source: BHF-UCL
Negative regulation of neuron death Source: Ensembl
Positive regulation of cell differentiation Source: Ensembl
Positive regulation of MAP kinase activity Source: BHF-UCL
Positive regulation of multicellular organism growth Source: BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
Positive regulation of receptor signaling pathway via JAK-STAT Source: GO_Central
Positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
Receptor internalization Source: BHF-UCL
Receptor signaling pathway via JAK-STAT Source: BHF-UCL
Regulation of multicellular organism growth Source: BHF-UCL
Response to cycloheximide Source: BHF-UCL
Response to estradiol Source: BHF-UCL
Response to food Source: Ensembl
Response to glucocorticoid Source: Ensembl
Response to interleukin-1 Source: Ensembl
Response to morphine Source: Ensembl
Taurine metabolic process Source: BHF-UCL

Cell membrane. On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway.
Isoform 2: Cell membrane. Remains fixed to the cell membrane and is not internalized.
Growth hormone-binding protein: Secreted. Complexed to a substantial fraction of circulating GH.

Laron syndrome (LARS):
A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.
Growth hormone insensitivity, partial (GHIP):
A disease characterized by partial resistance to growth hormone resulting in short stature. Short stature is defined by a standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for sex and chronological age, compared with a well-nourished, healthy, genetically relevant population.

Extracellular: 19-264
Helical: 265-288
Cytoplasmic: 289-638

The soluble form (GHBP) is produced by phorbol ester-promoted proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE. Shedding is inhibited by growth hormone (GH) binding to the receptor probably due to a conformational change in GHR rendering the receptor inaccessible to ADAM17 (By similarity).
On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2.
On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization (By similarity).