Activation of signal transducers and activators of transcription 1 and 3 by leukemia inhibitory factor, oncostatin-M, and interferon-gamma in adipocytes.
We have recently demonstrated that signal transducers and activators of transcription (STATs) 1, 3, 5A, 5B, and 6 are expressed in both cultured and native adipocytes. Our current studies have focused on the activation of STATs 1 and 3 by leukemia inhibitory factor (LIF), oncostatin-M (OSM), and interferon-gamma (IFNgamma) in 3T3-L1 adipocytes. IFNgamma is shown to be a potent activator of STAT 1 as indicated by both tyrosine phosphorylation and nuclear translocation. However, LIF and OSM, which are potent inducers of STAT 3, are less potent activators of STAT 1 as measured by both tyrosine phosphorylation and nuclear translocation. Both STATs 1 and 3 were translocated to the nucleus in a time-dependent fashion following LIF treatment. In addition, IFNgamma resulted in a time- and dose-dependent effect on STATs 1 and 3 nuclear translocation. Growth hormone, a potent activator of STATs 5A and 5B, had a minimal effect on STAT 1 and STAT 3 tyrosine phosphorylation. Preincubation with either insulin or growth hormone had no detectable effects on the tyrosine phosphorylation or nuclear translocation of STATs 1 and 3 induced by LIF, OSM, or IFNgamma. The effects of LIF and IFNgamma on STAT 1 and 3 tyrosine phosphorylation and nuclear translocation were confirmed in native rat adipocytes. In 3T3-L1 adipocytes, a low level of serine phosphorylation of STAT 3 on residue 727 was observed and was markedly enhanced by insulin, LIF, or OSM. This increase in STAT 3 Ser727 phosphorylation was dependent upon the activation of MAPK, since the MAPK kinase inhibitor (PD98059) reduced STAT 3 Ser727 phosphorylation to basal levels. The inhibition of MAPK had no effect on the ability of STATs 1 and 3 to be tyrosine-phosphorylated or translocate to the nucleus. These studies demonstrate the highly specific and quantitative activation of STATs 1 and 3 by LIF, OSM, and IFNgamma in adipocytes and indicate that STAT 3 is a substrate for MAPK in adipocytes.
Stephens
J M
JM
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. jsteph1@unix1.sncc.lsu.edu
Lumpkin
S J
SJ
Fishman
J B
JB
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D007328:Insulin; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; C508352:Osm protein, mouse; D010455:Peptides; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D053683:Oncostatin M; D014443:Tyrosine; D007371:Interferon-gamma; D013006:Growth Hormone; D017871:Calcium-Calmodulin-Dependent Protein Kinases