Figure 1.

TCR activation of Ca²⁺/DAG regulated kinases. T-cell receptor (TCR) ligation activates phopholipase Cγ (PLCγ), which cleaves phosphotidylinositol-(3,4)-bisphosphate (PIP₂) generating two key second messenger molecules, diacylglycerol (DAG) and inositol-(1,4,5)-trisphosphate (IP₃). IP₃ releases intracellular Ca²⁺ stores into the cytosol activating; the Ca²⁺ dependent phosphatase calcineurin inducing the expression of NFAT target genes, and the Ca²⁺ dependent kinase CaMKK which phosphorylates and activates AMPK and CaMK IV. The accumulation of DAG in the plasma membrane mediates the activation PKC and PKD protein kinases. DAG is also required for the activation of the Erk1/2 and RSK through activation of the Ras GTPase.