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

Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DAG) to terminate its signaling. To study DGKdelta, we disrupted its gene in mice and found that DGKdelta deficiency reduced EGF receptor (EGFR) protein expression and activity. Similar to EGFR knockout mice, DGKdelta-deficient pups were born with open eyelids and died shortly after birth. 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 substrates, and increased duanyu1531 autophosphorylation in DGKdelta knockout cells, indicating that DGKdelta regulates EGFR by modulating duanyu1531 signaling.

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