Modulation of STAT5 interaction with LMW-PTP during early megakaryocyte differentiation.
STATs are involved in a variety of cellular processes, including cell proliferation and differentiation. They are activated through tyrosine phosphorylation, which promotes their dimerization via SH2 domains. We have demonstrated previously that in DAMI megakaryoblastic cells LMW-PTP dephosphorylates STAT5, interacting with an essential sequence of nine amino acids in its C-terminal region. Here we characterize STAT5 tyrosine phosphorylation and its interaction with LMW-PTP during early phorbol-12-myristate-13-acetate-induced megakaryocyte differentiation; these processes show clear dependence on STAT5 threonine phosphorylation. Since protein kinase C inhibition prevents phorbol-12-myristate-13-acetate-induced STAT5 threonine phosphorylation and association with LMW-PTP, it follows that these processes depend on protein kinase C activity. By using a Thr757/Val mutant of STAT5 we also demonstrate that the 757 serine/threonine conserved residue, which is in the STAT5A region involved in the interaction with LMW-PTP, is essential for such an association, though its phosphorylation is not necessary.
Rigacci
Stefania
S
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, Florence 50134, Italy. rigacci@unifi.it
Guidotti
Valentina
V
Parri
Matteo
M
Berti
Andrea
A
D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D008970:Molecular Weight; D010766:Phosphorylation; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*
D050799:STAT5 Transcription Factor; D017027:Protein Tyrosine Phosphatases