MAP kinase activation in macrophages

Stimulation of macrophages by a variety of agents causes activation of mito gen-activated protein kinases (MAPKs). Activation of MAPKs by lipopolysacch aride involves CD14 and Toll receptors, Subsequent steps still remain to be explored. Tumor necrosis factor-alpha (TNF-alpha)-induced activation of MA PKs has been shown to involve the death domain proteins (TRADD, FADD, MADD) and TRAFs, Other molecules involved ill this pathway include the protein k inases, ASK1, germinal center kinase (GCK), hematopoietic progenitor kinase 1 (BPK1), and GCK-related kinase (GCKR), Although, these pathways have bee n described in various cell types, their role: in macrophages remains to be established. The availability of knockout mice and constitatively active a nd dominant-negative mutants of MAPKs should greatly enhance our understand ing of this field, The activation of MAPKs seems to be different in cell li nes compared with primary cells. Among the macrophages, cells from differen t compartments show different expression of receptors and signal transducti on molecules. These differences slay account for differences in MAPK activa tion and other phenotypic differences in macrophages frost different compar tments. Therefore, it is important to use primary cells for studying MAPK s ignal-transduction pathways, and the data from cell lines should not be ext rapolated to primary cells.