title: Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function.
abstract: 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.
authors.affiliation: Karolinska Institutet, Institutionen för Medicinsk Näringslära, NOVUM, Huddinge, Sweden.
authors.forename: P E
authors.initials: PE
authors.lastname: Lobie
authors.forename: G
authors.initials: G
authors.lastname: Allevato
authors.forename: J H
authors.initials: JH
authors.lastname: Nielsen
authors.forename: G
authors.initials: G
authors.lastname: Norstedt
authors.forename: N
authors.initials: N
authors.lastname: Billestrup
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D006224:Cricetinae; D015536:Down-Regulation; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D017354:Point Mutation; D014176:Protein Biosynthesis; D051381:Rats; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine
chemical_list: D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D014443:Tyrosine; D013006:Growth Hormone; D015500:Chloramphenicol O-Acetyltransferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007930:Leucine