Nuclear protein kinase C isoforms: key players in multiple cell functions?
A.M. Martelli1,2, I. Faenza1, A.M. Billi1, F. Falà1, L. Cocco1 and L. Manzoli1
1Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell Apparato Locomotore, Sezione di Anaotmie Umana, Cell Signalling Laboratory, Università di Bologna, Italy and 2Istituto per i Trapianti d'Organo e I'Immunocitologia del C.N.R., Sezione di Bologna c/o IOR, Bologna, Italy
Offprint requests to: Dr. Alberto M. Martelli, Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy. Fax: +39-0512091695. e-mail: amartell@biocfarm.unibo.it
Summary. Protein kinase C (PKC) isozymes are a family of serine/threonine protein kinases categorized into three subfamilies: classical, novel, and atypical. PKC isozymes, whose expression is cell type-specific and developmentally regulated, are key transducers in many agonist-induced signaling cascades. To date at least 10 different PKC isotypes have been identified and are believed to play distinct regulatory roles. PKC isoforms are catalytically activated by several lipid cofactors, including diacylglycerol. PKC is thought to reside in the cytoplasm in an inactive conformation and to translocate to the plasma membrane or cytoplasmic organelles upon cell activation by different stimuli. However, a sizable body of evidence collected over the last 15 years has shown PKC to be capable of translocating to the nucleus. Furthermore, PKC isoforms can reside within the nucleus. Studies from independent laboratories have to led to the identification of several nuclear proteins which act as PKC substrates as well as to the characterization of some nuclear PKC-binding proteins which may be of fundamental importance for finely tuning PKC function in this peculiar cell microenvironment. Most likely, nuclear PKC isozymes are involved in the regulation of several important biological processes such as cell proliferation and differentiation, neoplastic transformation, and apoptosis. In this review, we shall summarize the most intriguing evidence about the roles played by nuclear PKC isozymes. Histol. Histopathol. 18, 1301-1312 (2003)
Key words: Signal transduction, Phosphorylation, Proliferation,
Differentiation, Apoptosis
DOI: 10.14670/HH-18.1301