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.