Key result
Substitution of tyrosine residues 333 and 338 of the growth hormone receptor resulted in deficient lipogenesis and protein synthesis, while ligand binding and transcriptional regulation remained normal.
Specific tyrosine residues (333 and 338) of the growth hormone receptor are required for selected cellular responses to GH, such as lipogenesis and protein synthesis, but not for others like transcriptional regulation.
Distinguishes GH receptor domains for metabolic versus transcriptional effects in animals; leaves open relevance to human physiology or therapy.
We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine (CHO-GHR1-638 Y333F, Y338F) were generated by cDNA transfection. Compared with the wild type receptor the Y333F,Y338F mutant possessed normal high affinity ligand binding, hormone internalization, and ligand-induced receptor down-regulation. GH activation of mitogen-associated protein kinase was also similar in CHO clones expressing similar wild type and Y333F,Y338F receptor number. However, two GH-regulated cellular events (lipogenesis, and protein synthesis) were deficient in the tyrosine substituted receptor. In contrast, transcriptional regulation by GH (as evidenced by chloramphenicol acetyltransferase cDNA expression driven by the GH-responsive region of the SPI 2.1 gene) was not affected by Y333F,Y338F substitution. Thus we provide the first experimental evidence that specific tyrosine residues of the GH receptor are required for selected cellular responses to GH.
No takes yet. Share an insight, caveat, or question.
Lobie et al. (1995) studied this question. Substitution of tyrosine residues 333 and 338 for phenylalanine in the GH receptor vs. Wild type GH receptor was evaluated on Cellular response to GH (lipogenesis, protein synthesis, transcriptional regulation, MAPK activation). Substitution of tyrosine residues 333 and 338 of the growth hormone receptor resulted in deficient lipogenesis and protein synthesis, while ligand binding and transcriptional regulation remained normal.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: