PROTEIN-KINASE-C REGULATES THE NUCLEAR-LOCALIZATION OF DIACYLGLYCEROLKINASE-ZETA

Citation
Mk. Topham et al., PROTEIN-KINASE-C REGULATES THE NUCLEAR-LOCALIZATION OF DIACYLGLYCEROLKINASE-ZETA, Nature, 394(6694), 1998, pp. 697-700
Citations number
29
Categorie Soggetti
Multidisciplinary Sciences
Journal title
NatureACNP
ISSN journal
00280836
Volume
394
Issue
6694
Year of publication
1998
Pages
697 - 700
Database
ISI
SICI code
0028-0836(1998)394:6694<697:PRTNOD>2.0.ZU;2-5
Abstract
Diacylglycerol kinases (DGKs) terminate signalling from diacylglycerol by converting it to phosphatidic acid(1-8) Diacylglycerol regulates c ell growth and differentiation, and its transient accumulation in the nucleus may be particularly important in this regulation(9,10) Here we show that a fraction of DGK-zeta is found in the nucleus, where it re gulates the amount of nuclear diacylglycerol. Reducing nuclear diacylg lycerol levels by conditional expression of DGK-zeta attenuates cell g rowth. The nuclear-localization signal of DGK-zeta is located in a reg ion that is homologous to the phosphorylation-site domain of the MARCK S protein. This is, to our knowledge, the first evidence that this dom ain, which is a major target for protein kinase C, can localize a prot ein to the nucleus. Two isoforms of protein kinase C, but not others, regulate the localization of DGK-zeta. Our results define a cycle in w hich diacylglycerol activates protein kinase C, which then regulates t he metabolism of diacylglycerol by alternating the intracellular locat ion of DGK-zeta. This maybe a general mechanism to control mitogenic s ignals that depend on nuclear diacylglycerol.