STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation

Activation of the platelet-derived growth factor (PDGF) receptor tyrosine k inase induces tyrosine phosphorylation of Signal Transducer and Activator o f Transcription (STAT) proteins. Since the PDGF receptor also activates the Src tyrosine kinase, it is possible that Src mediates tyrosine phosphoryla tion of STATs in PDGF-treated cells. Consistent with a role for Src in STAT activation, we found that a PDGF receptor juxtamembrane tyrosine residue r equired for Src activation is necessary and sufficient for activation of ST ATs 1 and 3. To test the Src requirement further, we made other mutations i n the PDGF receptor juxtamembrane region that increased or decreased Src bi nding. In epithelial and fibroblast cells, PDGF activated STAT1, 3 and 6 in the absence of detectable binding and activation of Src. In addition, PDGF induced C-myc RNA expression and DNA synthesis even though Src was not det ectably activated. The activation of MAP kinase and the induction of c-fos gene expression both correlated with STAT but not Src activation by the rec eptor. We conclude that juxtamembrane tyrosine phosphorylation is necessary for both Src tyrosine kinase and STAT activation by the beta PDGF receptor , but that both processes are regulated independently by this region.