An alternative splicing form of dgkδ in muscle cells

Diacylglycerol (DAG) is a second messenger that activates Protein Kinase C (PKC). It also plays a central role in the biosynthesis of phospholipid. Diacylglycerol Kinase (DGK) is involved in the conversion of DAG to phosphatidic acid (PA). The activity of DGK influences the cellular level of DAG, which, in turn, affects cell growth and differentiation through PKC. A novel human DGK, DGKδ, was identified in our lab recently. It contains two zinc-fingers, a putative ATP-binding site and four ankyrin repeats at the carboxy-terminus. Human multiple tissue Northern blot shows that hDGKδ has a major transcript of 3.7 kb. Interestingly, an additional 4.2 kb transcript was detected in skeletal and heart muscle. We used the 3.7 kb hDGKδ cDNA as a probe to isolate a 4.2 kb cDNA clone from a skeletal muscle cDNA library. The protein product encoded by this 4.2 kb transcript contains all three domains of hDGKδ but has a unique N-terminal domain. We conclude that this is an alternatively spliced form of hDGKδ on the basis of sequence comparison and functional analysis. A 130 kD protein was detected by an anti-hDGKδ antibody in Cos7 cells transfected with the 4.2 kb cDNA. We found by immunochemical methods that this alternatively spliced transcript encodes a nuclear protein. Since this 4.2 kb transcript only exists in muscle cells, we speculate that this alternatively spliced transcript may be involved in the differentiation process of muscle cells.