Modulation and lack of cross-talk between signal transducer and activator of transcription 5 and Suppressor of cytokine signaling-3 in insulin and growth hormone signaling in 3T3-L1 adipocytes.
OBJECTIVE
To examine the role of signal transducer and activator of transcription (STAT) 5 and suppressor of cytokine signaling (SOCS)-3 in the cross-talk between growth hormone and insulin (INS) signaling in fat cells.


METHODS
Fully differentiated 3T3-L1 adipocytes were exposed to INS, growth hormone (GH), or both of these growth factors, and the activation of STAT5 proteins and mitogen-activated protein kinase was examined using phospho-specific antibodies. The induction of SOCS-3 mRNA was assessed by Northern blot analysis. INS-stimulated glucose transport was also measured.


RESULTS
We observed that GH, not INS, induced STAT5 activation in adipocytes in a manner that was independent of extracellular signal-regulated kinase (ERK) activation or new protein synthesis. GH strongly induced SOCS-3 mRNA expression, whereas INS had a much less potent effect on SOCS-3 mRNA expression. Because SOCS-3 has been implicated in the attenuation of GH and INS signaling, we examined the cross-talk between these signaling pathways. GH pretreatment of adipocytes inhibited GH signaling. Similarly, INS pretreatment inhibited INS signaling. However, INS did not block the GH-induced activation of STAT5, and GH did not block the INS induction of ERK activity or of increased glucose uptake. We observed that neither new protein synthesis nor activation of ERKs 1 and 2 were required for the inhibition of GH signaling.


CONCLUSIONS
These results demonstrate that blocking the induction of the SOCS-3 protein has no effect on the attenuation of GH signaling and support recent studies suggesting that SOCS proteins have additional functions. In addition, these studies demonstrate that GH-induced SOCS-3 expression is insufficient to inhibit INS-induced glucose uptake in adipocytes.
Story
David J
DJ
Department of Biological Sciences, Louisiana State University, 202 Life Sciences Building, Baton Rouge, LA 70803, USA.
Stephens
Jacqueline M
JM
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000493:pharmacokinetics; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D007328:Insulin; D009570:Nitriles; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C113580:U 0126; D013006:Growth Hormone; D003513:Cycloheximide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose