Mitogen-activated protein kinases in heart development and diseases.
Mitogen-activated protein (MAP) kinases belong to a highly conserved family of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological functions. The 4 best-characterized MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, have been implicated in different aspects of cardiac regulation, from development to pathological remodeling. Recent advancements in the development of kinase-specific inhibitors and genetically engineered animal models have revealed significant new insights about MAP kinase pathways in the heart. However, this explosive body of new information also has yielded many controversies about the functional role of specific MAP kinases as either detrimental promoters or critical protectors of the heart during cardiac pathological processes. These uncertainties have raised questions on whether/how MAP kinases can be targeted to develop effective therapies against heart diseases. In this review, recent studies examining the role of MAP kinase subfamilies in cardiac development, hypertrophy, and survival are summarized.
Wang
Yibin
Y
Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. yibinwang@mednet.ucla.edu
D000818:Animals; D030801:Animals, Genetically Modified; D002986:Clinical Trials as Topic; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D005318:Fetal Heart / Q000201:enzymology; D006330:Heart Defects, Congenital / Q000201:enzymology; D006331:Heart Diseases / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases