Growth Hormone Receptor (GHR) Antibody – Mouse Monoclonal

This gene encodes a member of the type I cytokine receptor family, which 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. 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. 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. Multiple alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jun 2011]

Function: 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.

Subunit structure: On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain

By similarity. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation

By similarity. Interacts with ADAM17

By similarity.

Subcellular location: Cell membrane; Single-pass type I membrane protein. Note: On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway

By similarity.Isoform 2: Cell membrane; Single-pass type I membrane protein. Note: Remains fixed to the cell membrane and is not internalized.Growth hormone-binding protein: Secreted. Note: Complexed to a substantial fraction of circulating GH

By similarity.

Tissue specificity: Expressed in various tissues with high expression in liver and skeletal muscle. Isoform 4 is predominantly expressed in kidney, bladder, adrenal gland and brain stem. Isoform 1 expression in placenta is predominant in chorion and decidua. Isoform 4 is highly expressed in placental villi. Isoform 2 is expressed in lung, stomach and muscle. Low levels in liver.

Domain: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.The box 1 motif is required for JAK interaction and/or activation.The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.

Post-translational modification: 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

By similarity.On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization

By similarity.

Polymorphism: Genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia [

MIM:143890] patients carrying a mutation in the LDLR gene.

Involvement in disease: Laron syndrome (LARS) [MIM:262500]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.23 Ref.26 Ref.28Short stature, idiopathic, autosomal (ISSA) [MIM:604271]: A condition 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, genetically relevant population, in the absence of specific causative disorders.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Sequence similarities: Belongs to the type I cytokine receptor family. Type 1 subfamily.Contains 1 fibronectin type-III domain.