Regulation of protein kinase C and epidermal growth factor receptor signaling by a diacylglycerol kinase delta

Diacylglycerol kinases (DGKs), which convert diacylglycerol (DAG) to phosphatidic acid (PA), consist of 10 isoforms divided into five subfamilies based on their distinct regulatory domains. The fact that DGK knockout mice from several subfamilies have different phenotype indicates that each DGK isotype has unique cellular function. DGK? is a type II diacylglycerol kinase with separated catalytic domain, a pleckstrin homology (PH) domain and a sterile ?-motif (SAM) domain. To study in vivo function of DGK?, knockout mouse model is generated by deletion of N-terminal portion of kinase catalytic domain. Mice with homozygous null mutation of DGK? displayed open eyelids, developed respiratory difficulty and died within 24 hours after birth. The phenotype of open eyelids is associated with EGFR signaling pathway. With further investigation, I characterized that DGK? deficiency leads to both inhibition of EGFR activity and reduction of EGFR expression.