TGF-β receptor signaling regulates phosphatidylinositol metabolism.
A, a model for the crosstalk between TCR and TGFβR signaling was constructed. Simulations were performed using a constant amount of TCR signal and varying amounts of TGFβR signal. B–E, the trajectories for (B) p-ZAP70, (C) PtdIns(4,5)P2, (D) PtdIns(3,4,5)P3, and (E) PtdIns(3,4)P2 are presented. CD4+ T cells isolated by negative selection were in vitro activated through TCR and CD28 costimulation for 10 min with various doses of TGF-β. F–H, imaging flow cytometry was utilized to measure the relative abundance of (F) PtdIns(4,5)P2, (G) PtdIns(3,4,5)P3, and (H) PtdIns(3,4)P2 normalized to the zero TGF-β data point. Shown are mean ± S.D. for three independent experiments.