title: The role of protein kinases in adaptational growth of the heart.
abstract: The ventricular myocyte is a terminally-differentiated cell that can no longer undergo cell division. In response to a variety of stimuli, including exposure to endothelin-1, phenylephrine or mechanical stretch, the myocyte increases its size and its complement of organized myofibrils. These adaptational changes during myocyte hypertrophy are accompanied by distinct changes in gene expression. The signalling cascades that initiate these changes are currently under intensive investigation. Many hypertrophic agonists activate protein kinase C (PKC). Transfection of ventricular myocytes with constitutively-active PKC isoforms initiates the changes in gene expression typical of the hypertrophic response. Similarly, the Ras/Raf/mitogen-activated protein kinase (MAPK) pathway can be activated by a variety of hypertrophic agents. Transfection of ventricular myocytes with components of this pathway has demonstrated that MAPK is essential for the changes in gene expression associated with the development of hypertrophy. However a Ras-dependent, but Raf-independent, pathway may regulate the organization of the contractile apparatus. Other protein kinases, such as ribosomal S6 kinases, p90RSK or p70/p85S6K, which are poorly characterized in the ventricular myocyte, may also regulate changes in gene expression. Further research is required to investigate cross-talk between these signal transduction pathways so that the spatial and temporal relationships that integrate the multiple signaling events leading to the adaptational growth of the ventricular myocyte may be understood.
authors.affiliation: National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Bogoyevitch
authors.forename: P H
authors.initials: PH
authors.lastname: Sugden
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology*; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000254:growth & development; D006801:Humans; D008934:Mitogens / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008934:Mitogens; D011494:Protein Kinases; D011493:Protein Kinase C