Effects of growth hormone antagonists on 3T3-F442A preadipocyte differentiation.
We have previously shown that a bovine (b) GH antagonist, bGH-M8, which possesses three amino acid substitutions in its third alpha-helix, inhibits mouse 3T3-F442A preadipocyte differentiation. In the current studies, we used the bGH and human (h) GH analogs with single amino acid substitution, bGH-G119R and hGH-G120R, for determining their biological activity using the preadipocyte differentiation assay. Short-term and long-term GH-inducible events were studied during adipose differentiation, including late marker gene expression (adipocyte protein 2), immediate early gene induction (c-fos), and tyrosine phosphorylation of intracellular proteins. The results demonstrated that these GH analogs not only failed to induce these three events, but also antagonized GH induction of c-fos expression and phosphorylation of proteins of apparent molecular mass of 95 kDa. Our present study agrees with the notion that GH must bind to the GH receptor via site one and with a second GH receptor molecule (or with some yet unidentified 'second target') through GH binding site two. This interaction is important for subsequent GH-dependent biological events.
Xu
B C
BC
Department of Biological Sciences, Ohio University, Athens 45701, USA.
Chen
W Y
WY
Gu
T
T
Ridgway
D
D
Wiehl
P
P
Okada
S
S
Kopchick
J J
JJ
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D018996:Myelin P2 Protein / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011994:Recombinant Proteins; D014443:Tyrosine / Q000378:metabolism
D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; C095717:G119R protein, human; C093172:G120R protein, human; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D014443:Tyrosine; D013006:Growth Hormone