TGF-BETA-1 SELECTIVELY SUPPRESSES PDGF RECEPTOR SIGNALING PATHWAYS INMG-63 HUMAN OSTEOSARCOMA CELL

We previously found that TGF-beta 1 inhibits PDGF mitogenicity in MG-6 3 cells and the inhibition is correlated with a suppression of the PDG F-induced receptor autophosphorylation. In this study, we analyze if a ll the PDGF receptor signaling pathways are similarly affected by the TGF-beta 1 pretreatment. We show that TGF-beta 1 suppresses PDGF-stimu lated tyrosine phosphorylation of PLC-gamma 1, and the phosphorylation of Erk. In contrast, the tyrosine phosphorylation of PI3-kinase is no t affected. Thus, TGF-beta 1 selectively suppresses two out of three P DGF receptor signaling pathways despit of its prominent inhibition of the PDGF-induced receptor autophosphorylation. The results also indica te that activation of the PI3-kinase pathway alone by PDGF is not suff icient in supporting the optimum growth of MG-63 cells under the cultu re conditions employed.