Fig. 5

Membrane events and generation of intracellular second messengers essential for TCR-induced mobilization of activators of transcription initiation and P-TEFb. During antigen presentation, maximal activation of TCR signaling requires a costimulatory engagement that usually involves a pairwise linkage between B7 and its T-cell counterpart CD28. TCR stimulation triggers a receptor and non-receptor phospho-tyrosine cascade that results in the generation of diacylglycerol (DAG), intracellular mobilization of calcium (Ca⁺⁺) from the endoplasmic reticulum (ER), and formation of phosphatidylinositol-3,4,5 triphosphate (PIP₃) which serves to anchor PDK1, AKT, and mTORC2 to the membrane. PLCγ-generated DAG initiates the membrane recruitment and activation of PKC-θ and RasGRP. DAG can be phosphorylated by diacylglycerol kinase (DGK), which leads to the curtailing of DAG signaling and the generation of an additional lipid second messenger phosphatidic acid (PA)