title: Insulin stimulates the serine phosphorylation of the signal transducer and activator of transcription (STAT3) isoform.
abstract: Insulin stimulation of Chinese hamster ovary cells expressing the human insulin receptor and differentiated 3T3L1 adipocytes resulted in a time-dependent reduction in the SDS-polyacrylamide gel electrophoretic mobility of STAT3. The decreased STAT3 mobility initially occurred by 2 min and was quantitative by 5 min. In addition, the change in STAT3 mobility was concentration-dependent and was detectable at 0.3 nm insulin with maximal effect between 1 and 3 nm. Although both these cell types also express the STAT1 alpha, STAT1 beta, STAT5, and STAT6 isoforms, only STAT3 was observed to undergo an insulin-dependent reduction in mobility. Immuno-precipitation of STAT1 and STAT3 from 32P-labeled cells demonstrated that only STAT3 was phosphorylated in response to insulin whereas phosphoamino acid analysis indicated that this phosphorylation event occurred exclusively on serine residues. Furthermore, treatment of cell extracts with alkaline phosphatase reversed the insulin-stimulated decrease in STAT3 mobility. Together, these data demonstrate that insulin is a specific activator of STAT3 serine phosphorylation without affecting the other STAT isoforms.
authors.affiliation: Department of Physiology and Biophysics, University of Iowa, Iowa City 52242-1109, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Ceresa
authors.forename: J E
authors.initials: JE
authors.lastname: Pessin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D012694:Serine / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D012694:Serine