A single arginine residue determines species specificity of the human growth hormone receptor.

摘要: Although growth hormone (GH) receptors (GHRs) in many species bind human (h) GH as well their own GH, the hGHR only binds primate GH. Arg43 interacts with Asp171 of hGH. Nonprimates have a His position equivalent to residue 171 and Leu 43 GHR. To determine whether accounts for specificity hGHR, point mutations that changed Leu43 Arg were introduced into cDNAs encoding bovine (b) GHR or rat binding protein (GHBP) these mutants wild-type (WT) counterparts expressed mouse L cells. Binding hGH bGH transfected cells GHBP secreted incubation medium was assessed by displacement 125I-labeled WT mutant bGHR bound similar affinity, but affinity reduced 200-fold. Likewise, equal bGH. Cross-linking produced 141-kDa labeled complex whose appearance blocked unlabeled hGH, cross-linking receptors. Both stimulated tyrosine phosphorylation 95-kDa GHR, less effective expressing We conclude incompatibility His171 nonprimate is major determinant specificity.