Purinergic activation of a tyrosine kinase-dependent pathway in cardiac cells

This overview focuses on the role of cytosoluble tyrosine kinases in the pu rinergic regulation of cardiac function. Cardiac cells express many cytosol ic tyrosine kinases, including pp60(c-src), p59(c-fyn) Csk, FAK, and Tec. P urinergic stimulation of cardiomyocytes increases the activity of pp60(c-sr c) and p59(c-fyn) and induces phosphorylation of FAK. This signaling pathwa y leads to phosphorylation of many proteins, including PLC gamma, the major PLC isoform in heart, and AE1, the predominant cardiac Cl/HCO3 exchanger. Tyrosine kinase-mediated phosphorylation of PLC gamma and AE1 allows the ca rdiomyocyte to regulate both its Ca2+ and H+ homeostasis, respectively. The existence of other cardiac intracellular substrates of tyrosine kinases, t argets of the purinergic stimulation as well as the physiological relevance of this signaling pathway, is discussed. Drug Dev. Res. 45:427-433, 1998. (C) 1998 Wiley-Liss, Inc.