Identification and Characterization of Two Splice Variants of Human Diacylglycerol Kinase η*

By T. Murakami, F. Sakane, S. Imai, K. Houkin, H. Kanoh. Journal of Biological Chemistry, 2003

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Diacylglycerol kinase (DGK) participates in regulating the intracellular concentrations of two bioactive lipids, diacylglycerol and phosphatidic acid. DGKη (η1, 128 kDa) is a type II isozyme containing a pleckstrin homology domain at the amino terminus. Here we identified another DGKη isoform (η2, 135 kDa) that shared the same sequence with DGKη1 except for a sterile α motif (SAM) domain added at the carboxyl terminus. The DGKη1 mRNA was ubiquitously distributed in various tissues, whereas the DGKη2 mRNA was detected only in testis, kidney, and colon. The expression of DGKη2 was suppressed by glucocorticoid in contrast to the marked induction of DGKη1. DGKη2 was shown to form through its SAM domain homo-oligomers as well as hetero-oligomers with other SAM-containing DGKs (δ1 and δ2). Interestingly, DGKη1 and DGKη2 were rapidly translocated from the cytoplasm to endosomes in response to stress stimuli. In this case, DGKη1 was rapidly relocated back to the cytoplasm upon removal of stress stimuli, whereas DGKη2 exhibited sustained endosomal association. The experiments using DGKη mutants suggested that the oligomerization of DGKη2 mediated by its SAM domain was largely responsible for its sustained endosomal localization. Similarly, the oligomerization of DGKη2 was suggested to result in negative regulation of its catalytic activity. Taken together, alternative splicing of the human DGKη gene generates at least two isoforms with distinct biochemical and cell biological properties responding to different cellular metabolic requirements.

Subfields: Biochemistry, Molecular Biology

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