Growth hormone receptor

Growth hormone receptor
PDB rendering based on 1a22.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1A22, 1AXI, 1HWG, 1HWH, 1KF9, 2AEW, 3HHR
Identifiers
Symbols	GHR ; GHBP; GHIP
External IDs	OMIM: 600946 MGI: 95708 HomoloGene: 134 ChEMBL: 1976 GeneCards: GHR Gene
Gene ontology Molecular function • cytokine receptor activity • protein binding • peptide hormone binding • growth factor binding • protein kinase binding • protein homodimerization activity • proline-rich region binding Cellular component • extracellular region • extracellular space • intracellular • plasma membrane • integral component of plasma membrane • cell surface • integral component of membrane • receptor complex • growth hormone receptor complex Biological process • activation of MAPK activity • allantoin metabolic process • citrate metabolic process • 2-oxoglutarate metabolic process • succinate metabolic process • oxaloacetate metabolic process • isoleucine metabolic process • valine metabolic process • creatine metabolic process • fatty acid metabolic process • endocytosis • JAK-STAT cascade • cytokine-mediated signaling pathway • taurine metabolic process • receptor internalization • response to estradiol • cellular response to hormone stimulus • regulation of multicellular organism growth • positive regulation of multicellular organism growth • positive regulation of tyrosine phosphorylation of Stat3 protein • positive regulation of tyrosine phosphorylation of Stat5 protein • activation of JAK2 kinase activity • multicellular organismal metabolic process • creatinine metabolic process • response to cycloheximide • insulin-like growth factor receptor signaling pathway • positive regulation of peptidyl-tyrosine phosphorylation • growth hormone receptor signaling pathway • JAK-STAT cascade involved in growth hormone signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2690	14600
Ensembl	ENSG00000112964	ENSMUSG00000055737
UniProt	P10912	P16882
RefSeq (mRNA)	NM_000163	NM_001048147
RefSeq (protein)	NP_000154	NP_001041643
Location (UCSC)	Chr 5: 42.42 – 42.72 Mb	Chr 15: 3.32 – 3.58 Mb
PubMed search	[1]	[2]

Growth hormone receptor is a protein that in humans is encoded by the GHR gene. GHR orthologs have been identified in most mammals.

This gene encodes a protein that is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization (the receptor may however also exist as a pre-assembled non-functional dimer ) 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 (proportional dwarfism). Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized. Laron mice (that is mice genetically engineered to carry defective Ghr), have a dramatic reduction in body mass (only reaching 50% of the weight of normal siblings), and also show a ~40% increase in lifespan.

Interactions

Growth hormone receptor has been shown to interact with SGTA, PTPN11, Janus kinase 2, Suppressor of cytokine signaling 1 and CISH.

Evolution

The GHR gene is used in animals as a nuclear DNA phylogenetic marker. The exon 10 has first been experienced to explore the phylogeny of the major groups of Rodentia. GHR has also proven useful at lower taxonomic levels, e.g., in octodontoid, arvicoline, muroid, murine, and peromyscine rodents, in arctoid and felid carnivores, and in dermopterans. Note that the GHR intron 9 has also been used to investigate the mustelid and hyaenid carnivores phylogenetics.

Antagonists

Growth hormone receptor antagonists such as pegvisomant (trade name Somavert) are used in the treatment of acromegaly. They are used if the tumor of the pituitary gland causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful. Pegvisomant is delivered as a powder that is mixed with water and injected under the skin.

External links

• Somatotropin receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
• Illustration at nih.gov
• Overview
• Growth Hormone Receptor: Molecule of the Month by Shuchismita Dutta and David Goodsell (April 2004)