The MARCKS family of cellular protein kinase C substrates.

Abstract

Stimulation of membrane polyphosphoinositol turnover is one of the most commonly employed signal transduction systems in normal physiology.The two second messengers generated by this reaction include inositol 1,4,5-trisphosphate, which can transiently elevate intracellular calcium levels, and diacylglycerols, which can activate most isoforms of protein kinase C (PKC).' Activation of members of this family of a t least 10 isoenzymes leads to a wide variety of physiological effects, including synthesis of macromolecules, activation of transport systems, secretion of hormones, contraction of muscle, and many others.However, the molecular steps between the activation of PKC and the resultant biological responses are largely unknown.One approach to elucidating these molecular pathways is to study direct cellular substrates for PKC in the hope that the knowledge gained will help to explain downstream events.This review will focus on one class of PKC substrates of which the prototype is the myristoylated, alanine-rich C kinase substrate or MARCKS protein.This protein, also referred to as 87 kDa, 80K, phosphomyristin, etc. has been employed for at least a decade as an indicator or marker for PKC activation in intact cells; early studies of this type have been reviewed previously (1,2).This review will concentrate on data that have accrued since the elucidation of the primary sequence of the protein, particularly potential structure:function relationships.