growth hormone receptor; GH receptor; somatotropin receptor; contains: growth hormone-binding protein; GH-binding protein; GHBP; serum-binding protein (GHR)

^[1]^[2]

Function

receptor for pituitary gland growth hormone
involved in regulating postnatal body growth
on ligand binding, couples to the JAK2/STAT5 pathway (putative)
the soluble form (GHBP) acts as a reservoir of growth hormone in plasma & may be a modulator/inhibitor of GH signaling
isoform 2 up-regulates the production of GHBP & acts as a negative inhibitor of GH signaling
on growth hormone (GH) binding, forms homodimers & binds JAK2 via a box 1-containing domain (putative)
binding to SOCS3 inhibits JAK2 activation
binding to CIS & SOCS2 inhibits STAT5 activation (putative)
interacts with ADAM17
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 (putative)
on GH binding, phosphorylated on Tyr in the cytoplasmic domain by JAK2 (putative)
on ligand binding, ubiquitinated on Lys in the cytoplasmic domain; this ubiquitination is not sufficient for GHR internalization (putative)

the WSXWS motif appears to be necessary for proper protein folding & thereby efficient intracellular transport & cell-surface receptor binding
the box 1 motif is required for JAK interaction &/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 & for its internalization
belongs to the type 1 cytokine receptor family, type 1 subfamily
contains 1 fibronectin F3 module

cell membrane
on growth hormone binding, GHR is ubiquitinated, internalized, down-regulated & transported into a degradative or non-degradative pathway (putative)
isoform 2: cell membrane remains fixed to the cell membrane & is not internalized
growth hormone-binding protein: secreted

named isoforms=4 Arises by species-specific retrovirus-mediated alternative splice mimicry

high expression in liver & skeletal muscle
isoform 4 is predominantly expressed in kidney, bladder, adrenal gland & brain stem
in the placenta, isoform 1 predominantly expressed in chorion & decidua, isoform 4 highly expressed in villi
isoform 2 is expressed in lung, stomach & muscle
low levels in liver

defects in GHR are a cause of laron dwarfism
defects in GHR may be a cause of short stature
disruption of the gene for growth hormone receptor results in a longer life span in rats

genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia patients carrying a mutation in the LDLR gene