THE ROLE OF PROTEIN-KINASES IN ADAPTATIONAL GROWTH OF THE HEART

The ventricular myocyte is a terminally-differentiated cell that can n o longer undergo cell division, In response to a variety of stimuli, i ncluding exposure to endothelin-l, phenylephrine or mechanical stretch , the myocyte increases its size and its complement of organized myofi brils, These adaptational changes during myocyte hypertrophy are accom panied by distinct changes in gene expression, The signalling cascades that initiate these changes are currently under intensive investigati on, Many hypertrophic agonists activate protein kinase C (PKC), Transf ection 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 (MAP K) pathway can be activated by a variety of hypertrophic agents, Trans fection of ventricular myocytes with components of this pathway has de monstrated that MAPK is essential for the changes in gene expression a ssociated with the development of hypertrophy, However a Ras-dependent , but Raf-independent, pathway may regulate the organization of the co ntractile apparatus, Other protein kinases, such as the ribosomal S6 k inases, p90(RSK) or P70/P85(S6K), which are poorly characterized in th e ventricular myocyte, may also regulate changes in gene expression, F urther research is required to investigate cross-talk between these si gnal transduction pathways so that the spatial and temporal relationsh ips that integrate the multiple signalling events leading to the adapt ational growth of the ventricular myocyte may be understood.