The role of MAP kinases in endothelial activation

Activation of endothelial cells by proinflammatory stimuli results in increased migration of leukocytes across the endothelium, which contributes to the progression of atherosclerosis. Thus, control of the inflammatory status of endothelial cells, which is achieved by a balance of pro- and antiinflammatory signals, is crucial to limiting the disease. The mitogen-activated protein kinases (MAPKs) are a family of central signaling molecules that respond to numerous stimuli by phosphorylating a variety of substrates including transcription factors, enzymes, and other kinases. While the extracellular signal-related kinases (ERK1/2) and big MAPK-1 (BMK1) are primarily involved in growth and cytoprotective functions, Jun amino-terminal kinases (JNK) and p38 proteins play an important role in inflammatory and stress responses. Because they have contradictory roles, the relative activation of these proteins is important to the inflammatory status of the cell. Additionally, there is known to be a crosstalk between MAPK cascades whereby the activity of one MAPK can be influenced by another. Thus, these proteins collectively integrate the pro- and antiinflammatory stimuli acting on the cell to produce the appropriate downstream effects. Here we review the roles of the MAPKs and the implications of MAPK crosstalk on endothelial activation.