[Truncated growth hormone receptor mutations function as dominant-negative inhibitors of the full-length receptor and cause genetic short stature].
Truncated growth hormone receptor (GHR) mutations that lack the majority of the cytoplasmic domain have been identified in familial short stature and same truncated GHR isoforms generated by alternative splicing in a number of normal human tissues. The binding affinity of the truncated GHR was similar to that seen for the full-length receptor and the truncated GHR showed a much greater expression on the cell surface, which is consistent with lack of internalization. These truncated receptors function as dominant-negative inhibitors of the growth hormone (GH) signal and generate large amounts of GH binding protein (GHBP). Thus, truncated GHR isoform may be important as a physiological regulator of GH signaling in addition to providing a mechanism for the production of GHBP.
Minamitani
Kanshi
K
Department of Pediatrics, Chiba Municipal Kaihin Hospital.
D004393:Dwarfism, Pituitary / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000235:genetics*
D017978:Receptors, Growth Factor