Diacylglycerol kinase δ regulates protein kinase C and epidermal growth factor receptor signaling.

Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DAG) to terminate its signaling. To study DGKδ, we disrupted its gene in mice and found that DGKδ deficiency reduced EGF receptor (EGFR) protein expression and activity. Similar to EGFR knockout mice, DGKδ-deficient pups were born with open eyelids and died shortly after birth. PKCs are activated by DAG and phosphorylate EGFR to reduce its expression and activity. We found DAG accumulation, increased threonine phosphorylation of EGFR, enhanced phosphorylation of other PKC substrates, and increased PKC autophosphorylation in DGKδ knockout cells, indicating that DGKδ regulates EGFR by modulating PKC signaling. [ABSTRACT FROM AUTHOR]