Role of raf proteins in cardiac hypertrophy and cardiomyocyte survival.
Cardiomyocyte survival and growth are regulated by the action of extracellular ligands that activate intracellular signaling cascades. The Raf family of protein serine/threonine kinases plays a critical role in the regulation of cardiomyocyte survival and growth. The three Raf family members, Raf-1, B-Raf, and A-Raf, are highly homologous, and they are all expressed in the heart. Protein kinases of the Raf family phosphorylate and activate the mitogen-activated protein kinase kinases (MKKs, also known as MEKs). MKKs, in turn, are dual-specificity threonine and tyrosine kinases that phosphorylate and activate extracellular signal-regulated kinases (ERKs). ERKs phosphorylate a variety of substrates, including nuclear transcription factors, which regulate cell physiology. Raf proteins also have antiapoptotic activity that is independent of MKK and ERK. In this review, the role of Raf family members in the regulation of cardiomyocyte survival and growth will be discussed.
Muslin
Anthony J
AJ
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA. amuslin@im.wustl.edu
D000818:Animals; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology*; D010766:Phosphorylation; D048491:Proto-Oncogene Proteins A-raf / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D048491:Proto-Oncogene Proteins A-raf; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases