STAT 1alpha/1beta, STAT 3 and STAT 5: expression and association with c-MET and EGF-receptor in long-term cultures of human hepatocytes.
Long-term cultures of human hepatocytes were maintained serum-free in a chemically defined medium in the presence of HGF and EGF for up to 30 days. STAT 1alpha/1beta, STAT 3, and STAT 5 were present and tyrosine phosphorylated throughout the culture period in the cytosol as well as the nucleus. We show by co-immunoprecipitation that a portion of the cellular pools of STAT 1alpha/1beta and STAT 5 is physically associated with c-MET and EGF-receptor. Co-immunoprecipitation of STAT 3 with STAT 5 did occur in the cytosol but not in the nucleus, suggesting dimerization of the two STAT family members. The observed differences of protein amounts and tyrosine phosphorylation between cytosol and nucleus, the association of STAT proteins with EGF-receptor and c-MET and with each other may all be involved in regulating the activity of the STAT transcription factors. It is intriguing to speculate that STAT 5 may have a modulating role in the regulation of STAT 3 activity.
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Institut für Umwelttoxikologie, Innere Medizin, Martin-Luther Universität Halle-Wittenberg, Franzosenweg 1a, Halle/Saale, D-06097, Germany.
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Foth
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Michalopoulos
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D000818:Animals; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011817:Rabbits; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014443:Tyrosine; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met