Abstract
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. 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 DGKdelta knockout cells, indicating that DGKdelta regulates EGFR by modulating PKC signaling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Diacylglycerol Kinase / genetics
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Diacylglycerol Kinase / metabolism*
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Diglycerides / metabolism
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Enzyme Activation
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Female
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Gene Deletion
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Keratinocytes / cytology
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Keratinocytes / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phenotype
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Phosphorylation
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Protein Kinase C / genetics
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Protein Kinase C / metabolism*
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Signal Transduction / physiology*
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Threonine / metabolism
Substances
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Diglycerides
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Intercellular Signaling Peptides and Proteins
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Isoenzymes
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Threonine
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Diacylglycerol Kinase
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ErbB Receptors
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Protein Kinase C
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JNK Mitogen-Activated Protein Kinases