Physiological Reviews, Vol. 81, No. 2, April 2001, pp. 807-869
Copyright ©2001 by the American Physiological Society
Mammalian Mitogen-Activated Protein Kinase Signal
Transduction Pathways Activated by Stress and Inflammation
John M.
Kyriakis and
Joseph
Avruch
Diabetes Research Laboratory, Medical Services, and
Department of Molecular Biology, Massachusetts General Hospital,
and Department of Medicine, Harvard Medical School, Boston,
Massachusetts
Kyriakis, John M. and
Joseph Avruch.
Mammalian Mitogen-Activated Protein Kinase Signal
Transduction Pathways Activated by Stress and Inflammation. Physiol. Rev. 81: 807-869, 2001.
The molecular details of mammalian
stress-activated signal transduction pathways have only begun to be
dissected. This, despite the fact that the impact of these pathways on
the pathology of chronic inflammation, heart disease, stroke, the
debilitating effects of diabetes mellitus, and the side effects of
cancer therapy, not to mention embryonic development, innate and
acquired immunity, is profound. Cardiovascular disease and diabetes
alone represent the most significant health care problems in the
developed world. Thus it is not surprising that understanding these
pathways has attracted wide interest, and in the past 10 years,
dramatic progress has been made. Accordingly, it is now becoming
possible to envisage the transition of these findings to the
development of novel treatment strategies. This review focuses on the
biochemical components and regulation of mammalian stress-regulated
mitogen-activated protein kinase (MAPK) pathways. The nuclear
factor-
B pathway, a second stress signaling paradigm, has been the
subject of several excellent recent reviews (258, 260).
