Protein myristoylation as an intermediate step during signal transduction in macrophages: its role in @entity1426 metabolism and in responses to XXXX .

@entity32 @entity18257 @entity19 @entity60 @entity1426 @entity7131 @entity4996
The role of macrophages in the regulation of @entity32 and immunity is, in part, due to their secretory repertoire. Among the important mediators released by macrophages are the products of both the cyclooxygenase and lipoxygenase pathways of @entity1426 (20:4) metabolism. The principal focus of this paper is the mechanism by which bacterial lipopolysaccharides (LPS) regulate 20:4 metabolism in macrophages. LPS has the capacity to prime macrophages for greatly enhanced @entity19 metabolism when the cells are subsequently challenged with a spectrum of triggers. Concomitant with priming, LPS also promotes the covalent attachment of @entity18257 to a set of macrophage proteins. The time and concentration dependence of LPS-induced protein myristoylation is consistent with a role for myristoylation in LPS priming of the 20:4 cascade. One of the myristoylated proteins is a 68K (K = 10(3) Mr) @entity7131 substrate which associates with membranes upon myristoylation. LPS-primed macrophages show greatly increased phosphorylation of the 68K protein when the cells are subsequently treated with @entity7131 activating @entity4996 . It is proposed that the myristoylation of the 68K protein promotes its attachment to the membrane where it is more closely associated with activated @entity7131 ( @entity7131 ), an association which would ensure more efficient catalysis during the mobilization and oxygenation of 20:4. This paper also examines protein myristoylation during T-cell-mediated activation of macrophages. Immune-activated macrophages have an enhanced capacity to kill several infectious agents by oxidative mechanisms. The lymphokine gamma-interferon ( @entity60 ) rapidly induces the myristoylation of a 48K protein. This 48K protein is also myristoylated in @entity19 macrophages that have been activated in vivo by intraperitoneal injection of Corynebacterium parvum, suggesting that it may be an important intermediate in the activation of macrophages for enhanced microbicidal capacity.
