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Diacylglycerol kinase δ and sphingomyelin synthase-related protein functionally interact via their sterile α motif domains.
Murakami, Chiaki; Hoshino, Fumi; Sakai, Hiromichi; Hayashi, Yasuhiro; Yamashita, Atsushi; Sakane, Fumio.
Afiliación
  • Murakami C; Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan.
  • Hoshino F; Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan.
  • Sakai H; Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Organization for Research and Academic Information, Shimane University, Izumo 693-8501, Japan.
  • Hayashi Y; Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo 173-8605, Japan.
  • Yamashita A; Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo 173-8605, Japan.
  • Sakane F; Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan. Electronic address: sakane@faculty.chiba-u.jp.
J Biol Chem ; 295(10): 2932-2947, 2020 03 06.
Article en En | MEDLINE | ID: mdl-31980461
The δ isozyme of diacylglycerol kinase (DGKδ) plays critical roles in lipid signaling by converting diacylglycerol (DG) to phosphatidic acid (PA). We previously demonstrated that DGKδ preferably phosphorylates palmitic acid (16:0)- and/or palmitoleic acid (16:1)-containing DG molecular species, but not arachidonic acid (20:4)-containing DG species, which are recognized as DGK substrates derived from phosphatidylinositol turnover, in high glucose-stimulated myoblasts. However, little is known about the origin of these DG molecular species. DGKδ and two DG-generating enzymes, sphingomyelin synthase (SMS) 1 and SMS-related protein (SMSr), contain a sterile α motif domain (SAMD). In this study, we found that SMSr-SAMD, but not SMS1-SAMD, co-immunoprecipitates with DGKδ-SAMD. Full-length DGKδ co-precipitated with full-length SMSr more strongly than with SMS1. However, SAMD-deleted variants of SMSr and DGKδ interacted only weakly with full-length DGKδ and SMSr, respectively. These results strongly suggested that DGKδ interacts with SMSr through their respective SAMDs. To determine the functional outcomes of the relationship between DGKδ and SMSr, we used LC-MS/MS to investigate whether overexpression of DGKδ and/or SMSr in COS-7 cells alters the levels of PA species. We found that SMSr overexpression significantly enhances the production of 16:0- or 16:1-containing PA species such as 14:0/16:0-, 16:0/16:0-, 16:0/18:1-, and/or 16:1/18:1-PA in DGKδ-overexpressing COS-7 cells. Moreover, SMSr enhanced DGKδ activity via their SAMDs in vitro Taken together, these results strongly suggest that SMSr is a candidate DG-providing enzyme upstream of DGKδ and that the two enzymes represent a new pathway independent of phosphatidylinositol turnover.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Transferasas (Grupos de Otros Fosfatos Sustitutos) / Diacilglicerol Quinasa Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Transferasas (Grupos de Otros Fosfatos Sustitutos) / Diacilglicerol Quinasa Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: Japón