Protein kinase C isoforms and lipid second messengers: a critical nuclear partnership?
L.M. Neri1,2, P. Borgatti1, S. Capitani1,3 and A.M. Martelli2,4
1Dipartimento di Morfologia ed Embriologia, Sezione di Anatomia Umana, Università di Ferrara, Ferrara, Italy, 2Istituto di Citomorfologia Normale e Patologica del C.N.R., c/o I.O.R., Bologna, Italy, 3Interdisciplinary Center for the Study of Inflammation, Università di Ferrara, Ferrara, Italy and 4Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Sezione di Anatomia, School of Pharmacy, Università di Bologna, Bologna, Italy
Offprint requests to: Dr. Luca Neri, M.D., Dipartimento di Morfologia ed Embriologia, Sezione di Anatomia Umana, Universitá di Ferrara, via Fossato di Mortara 66, 44100 Ferrara, Italy. Fax: +39-051-443045. e-mail: l.neri@dns.unife.it
Summary. A growing body of evidence, accumulated over
the past 15 years,has highlighted that the protein kinase C family
of isozymes is capable of translocating to the nucleus or is resident
within the nucleus. The comprehension of protein kinase C isoform
regulation within this organelle is under development. At present,
it is emerging that lipid second messengers may play at least
two roles in the control of nuclear protein kinase C: on one side
they serve as chemical attractants, on the other they directly
modulate the activity of specific isoforms.
One of the best characterized lipid second messenger that could
be involved in the regulation of nuclear PKC activity is DAG.
The existence of two separate pools of nuclear DAG suggests that
this lipid second messenger might be involved in distinct pathways
that lead to different cell responses.
Nuclear phosphatidylglycerol, D-3 phosphorylated inositol lipids
and nuclear fatty acids are involved in a striking variety of
critical biological functions which may act by specific PKC activation.
The fine tuning of PKC regulation in cells subjected to proliferating
or differentiating stimuli, might prove to be of great interest
also for cancer therapy, given the fact that PKC-dependent signaling
pathways are increasingly being seen as possible pharmacological
target in some forms of neoplastic diseases.
In this article, we review the current knowledge about lipid
second messengers that are involved in regulating the translocation
and/or the activity of different protein kinase C isoforms identified
at the nuclear level. Histol. Histopathol. 17, 1311-1316 (2002)
Key words: Lipid second messengers, Protein kinase C,
Nucleus, Diacylglycerol, Phospholipase
DOI: 10.14670/HH-17.1311