Polyamine-mediated protein phosphorylations: a possible target for intracellular polyamine action

Abstract

Polyamines are well-known ubiquitous components of living cells. Although these polycations have been implicated in the regulation of major cellular functions such as DNA, RNA and protein synthesis occurring during cellular proliferation and/or differentiation processes, their mechanism of action at the molecular level has remained obscure. On the other hand, protein phosphorylation has emerged as a regulatory process of prime importance in cellular regulation. Data have recently been presented suggesting that polyamines may express at least part of their biological action through an effect upon selective protein phosphorylation systems. Two types of polyamine-sensitive protein kinases have been characterized in the last few years. The best known in molecular terms is the widespread casein kinase G (also termed casein kinase II), which represents a multifunctional protein kinase, at present classified as a messenger-independent activity. The other is a polyamine-dependent nuclear ornithine decarboxylase kinase characterized in Physarum polycephalum and several mammalian tissues. Both protein kinases are activated by polyamines in vitro at concentrations compatible with a physiological role, by a mechanism which most likely also involves an effect through the protein substrate conformation. Preliminary evidence suggests that both kinases may be implicated in the regulation of DNA-dependent RNA polymerase activities, although several other potential substrates have been suggested for casein kinase G. Another suggestion is that these kinases may also participate in the post-translational regulation of ornithine decarboxylase, the rate-limiting step in the polyamine biosynthetic pathway. A novel class of protein kinase activities may thus be defined as polyamine-mediated phosphorylation systems for which polyamines may function as intracellular messenger. Although their biological significance remains to be fully established, especially with regard to the definition of their specific intracellular target(s) and subsequent biological functions, these systems will be interesting to consider in future studies aimed at understanding the role of polyamines in cell regulation.