MAPK signaling and the kidney

Following an overview of the biochemistry of mitogen-activated protein kina se (MAPK) pathways, the relevance of these signaling events to specific mod els of renal cell function and pathophysiology, both in vitro and in vivo, will be emphasized. In in vitro model systems, events activating the princi pal MAPK families [extracellular signal-regulated and c-Jun NH2-terminal ki nase and p38] have been best characterized in mesangial and tubular epithel ial cell culture systems and include peptide mitogens, cytokines, lipid med iators, and physical stressors. Several in vivo models of proliferative or toxic renal injury are also associated with aberrant MAPK regulation. It is anticipated that elucidation of downstream effector signaling mechanisms a nd a clearer understanding of the immediate and remote upstream activating pathways, when applied to these highly clinically relevant model systems, w ill ultimately provide much greater insight into the basis for specificity now seemingly absent from these signaling events.