Stat5 is a physiological substrate of the insulin receptor.
Using the cytoplasmic domain of the insulin receptor (IR) in a yeast two-hybrid screen, we identified a cDNA clone encoding the C-terminal 308 amino acids of human Stat5b (Stat5b-Ct). Stat5b-Ct is tyrosine phosphorylated by purified IR kinase domain in vitro. Insulin stimulates tyrosine phosphorylation of overexpressed Stat5b-Ct and endogenous Stat5 in cells overexpressing IR. Stat5 may be a direct target of the IR and, as a member of the Stat family of transcription factors, may play a role in the regulation of gene transcription by insulin. In support of this hypothesis, perfusion of mouse liver with insulin promotes rapid tyrosine phosphorylation of Stat5 and activation of Stat5 DNA binding. Moreover, refeeding of fasted mice leads to rapid tyrosine phosphorylation and stimulation of enhanced DNA-binding activity of Stat5 extracted from liver, skeletal muscle, and adipose tissues. Taken together, our data strongly suggest that IR interacts with and phosphorylates Stat5 in vitro and in tissues physiologically sensitive to insulin.
Chen
J
J
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Sadowski
H B
HB
Kohanski
R A
RA
Wang
L H
LH
D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D005215:Fasting; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D008894:Milk Proteins; D009928:Organ Specificity; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D050799:STAT5 Transcription Factor; D012441:Saccharomyces cerevisiae; D013379:Substrate Specificity; D015534:Trans-Activators / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D007328:Insulin; D008894:Milk Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D011972:Receptor, Insulin