Myristoylated alanine-rich C-kinase substrate (MARCKS) is a predominentcellular substrate for protein kinase C (PKC) that has been implicated in the regulation of brain development, macrophage activation, neuro-secretion and growth factor-dependentmitogenesis [, ]. The N-terminal glycine is the site of myristoylation, which allows effective binding of the protein to the plasma membrane, whereit co-localises with PKC []. MARCKS binds calmodulin in a calcium-dependentmanner; the region responsible for calcium-binding is highly basic, a domainof about 25 amino acids known as the PSD or effector domain, which also contains the PKCphosphorylation sites and has been shown to contribute to membrane binding. When not phosphorylated, the effector domain can bindto filamentous actin []. It is believed that MARCKS may be a regulated crossbridge between actin and the plasma membrane; modulation of the actincross-linking activity by calmodulin and phosphorylation, represent apotential convergence of the calcium-calmodulin and PKC signal transductionpathways in regulation of the actin cytoskeleton. MARCKS also contains an MH2 domain of unknown function.MARCKS-related protein (MRP) is similar to MARCKS in terms of propertiessuch as its myristoylation, phosphorylation and calmodulin-binding, andshares a high degree of sequence similarity. The two regions that show the highestsimilarity are the kinase C phosphorylation site domain and the N-terminalregion containing the myristoylation site []. MARCKS and MRP amino acid compositions are similar, but the alanine content of the latter is lower. MARCKS proteins appear to adopt a native unfolded conformation i.e. as randomly folded chains arranged in non-classical extended conformations, in common with other substrates of PKC.
