Mitogen Activated Protein Kinases MAPKs

Mitogen-activated protein kinases are involved in multiple cascades of serine/threonine and tyrosine phosphory-lating reactions that mediate diverse cellular responses to growth factors, physical stress, and cytokines. The most studied MAPKs in mammalian cells are extracellular signal-related kinases (ERK 1/2), c-jun N-terminal kinases (JNK), and p38 proteins. Although ERK 1/2 is mainly known for its role in cell growth and p38 MAPK plays a major role in cellular responses to stress and injury, both have been implicated in the regulation of vascular endothelial permeability. A typical case is seen in endothelial cells or intact microvas-culature subjected to VEGF stimulation: Inhibition of ERK 1/2 with the ERK kinase inhibitor PD98059 or inhibition of p38 with SB203580 blocks VEGF-induced increases in permeability. In addition to the growth factor, many inflammatory agonists, including histamine, thrombin, hydrogen peroxide, and intracellular calcium elevating agents, are able to phosphorylate ERK 1/2. In parallel, the same types of substances have been found to induce endothelial cytoskeletal contraction and junctional barrier failure through a p38-related mechanism. Clearly, activation of either the ERK 1/2 or the p38 pathway can cause changes in endothelial barrier function; however, their relative contribution may vary depending on the form of stimulation, type of vessels, and duration of observations.

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Post a comment