STAT 1 alpha/1 beta 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 che mically defined medium in the presence of HGF and EGF for up to 30 days. ST AT 1 alpha/1 beta, STAT 3, and STAT 5 were present and tyrosine phosphoryla ted 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 STA T 1 alpha/1 beta and STAT 5 is physically associated with c-MET and EG;F-re ceptor, Co-immunoprecipitation of STAT 3 with STAT 5 did occur in the cytos ol but not in the nucleus, suggesting dimerization of the two STAT family m embers. The observed differences of protein amounts and tyrosine phosphoryl ation between cytosol and nucleus, the association of STAT proteins with EG F-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 specula te that STAT 5 may have a modulating role in the regulation of STAT 3 activ ity. (C) 1999 Academic Press.