Signal transduction by the phosphatidylinositol cycle in myocardium.
Diverse and distinct hormonal stimuli arriving at the cardiomyocyte engage specific surface receptors to initiate hydrolysis of inositol phospholipids by phospholipase C whereby information flows from changes in intracellular levels of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, 1,2-diacylglycerol and Ca2+ to the specific phosphorylation of cellular proteins by various protein kinases such as the protein kinase C family, Ca(2+)-calmodulin-dependent kinase and mitogen activated kinases. The phosphorylation products are potential regulators of the inotropic and chronotropic state, hypertrophic growth and specific gene expression and ischemic preconditioning of the myocardium. This review summarizes the current state of knowledge concerning the phosphatidylinositol cycle and its potential role in mediating various functional responses in myocardium. The multiplicity of receptor types, G-proteins, phospholipases C and protein kinases raises fundamental questions about the mechanisms that assure the precision and timing of the myocardial response to hormonal stimuli.
De Jonge
H W
HW
Department of Biochemistry, Faculty of Medicine & Health Sciences, Erasmus University Rotterdam, The Netherlands.
Van Heugten
H A
HA
Lamers
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism*; D008322:Mammals; D009206:Myocardium / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D004075:Diglycerides; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018160:Receptors, Cytoplasmic and Nuclear; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium