C-SRC ACTIVATES BOTH STAT1 AND STAT3 IN PDGF-STIMULATED NIH3T3 CELLS

Treatment of cells with PDGF and EGF specifically induces STAT1 and ST AT3, which became phosphorylated on tyrosine residues to form home and heterodimers: in these configurations they translocate into the nucle us where they act as transcription activators. However little is known about the activation of STATs in growth factor receptor signal transd uction. Recently it has been shown that v-Src modulates the tyrosine p hosphorylation of STAT3 but not of STAT1. Here we report that the cell ular Src tyrosine kinase is involved in the activation of both STAT1 a nd STAT3 in PDGF stimulated NIH3T3 cells. Both tyrosine phosphorylatio n and DNA binding activity of STAT1 and STAT3 are up-regulated in c-Sr c overexpressing cells, while we observe the opposite phenomenon in ce lls overexpressing the dominant negative Src. Furthermore, our results show that STAT1 co-immunoprecipitates with c-Src, suggesting that the activation of STATs by Src occurs via a direct interaction. Taken tog ether, these data suggest that c-Src is involved in activation of both STAT1 and 3 in PDGF signal transduction. (C) 1997 Academic Press.