Phosphorylation of diacylglycerol kinase-zeta by protein kinase C regulates its interaction with the PDZ domain of syntrophins

TL;DRAbstract

Diacylglycerol kinase-zeta (DGK-zeta) attenuates diacylglycerol (DAG) signaling by converting it into phosphatidic acid (PA). DGK-zeta binds via its C-terminus, which contains a PSD-95/ Discs-Large/ZO-1 (PDZ)-binding motif, to a family of PDZ domain-containing scaffold proteins called syntrophins. Previous studies showed that some PDZ-mediated interactions are regulated by phosphorylation of the C-terminal PDZ-binding motif, however, to my knowledge, there are no published reports which demonstrate that a phosphorylation outside of this motif regulates PDZ interactions. Here, I provide evidence that protein kinase C-mediated phosphorylation of the MARCKS domain of DGK-zeta increases its association with syntrophins by a PDZ-dependent mechanism. Compared to wild-type (wt) DGK-zeta, a mutant mimicking phosphorylation of the MARCKS domain (DGK-zeta M1) bound more to recombinant syntrophin PDZ domains in in vitro binding assays. Moreover, more endogenous syntrophin co-immunoprecipitated fr

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