A Diversity of Elements in the Protein Kinase C Signal Transduction Pathway

Abstract

Historically the discovery of this signalling system draws upon the convergence of two areas of research. The first was directed at the phenomenon of agonist induced inositol lipid turnover (reviewed in (Hokin, 1985)); the second was directed at the discovery and characterization of protein kinases with signalling potential, which lead to the identification of a calcium and phospholipid-dependent protein kinase termed protein kinase C (PKC) (see (Nishizuka, 1986; Nishizuka, 1988)). The critical link between these fields is the now established second messenger diacyglycerol (DAG) which is produced during agonist stimulated inositol lipid hydrolysis (by an inositol lipid-specific phospholipase C — Ptdlns- PLC) and is itself responsible for the activation of PKC (figure 1). The inositol 1,4,5 trisphosphate head group which is concurrently produced on degradation of Ptdlns 4,5 bisphosphate also serves a second messenger role in the release of Ca²⁺ from intracellular stores (Streb et. al., 1983). That DAG leads to PKC activation in vivo is evidenced by a variety of reports that short chain membrane permeable DAGs can activate PKC in intact cells as judged by the phosphorylation of particular proteins (e.g. (Kawahara et. al., 1980)). Furthermore such proteins can become phosphorylated in response to agonists that stimulate Ptdlns breakdown providing evidence for a causal role in the events of agonist induced cellular responses.