Transforming growth factor-β1 modulates adenylyl cyclase signaling elements and epidermal growth factor signaling in cardiomyocytes

✍ Scribed by Bipin G. Nair; Yiming Yu; Hani M. Rashed; Hui Sun; Tarun B. Patel

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 898 KB
• Volume: 164
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041640203

✦ Synopsis

Studies presented in this report were designed to investigate the effects of transforming growth factor-pl (TGF-01) on epidermal growth factor (EGF)mediated stimulation of CAMP accumulation in cardiac myocytes and elucidate the mechanism(s) involved in this modulation. TGF-PI (20 pM) treatment of cardiac myocytes, in a time-dependent manner, decreased the ability of EGF (100 nM) to increase CAMP accumulation. Significant attenuation of EGFelicited CAMP accumulation was observed 2 h after exposure to TGF-PI and 18 h after addition of TGF-p1, the ability of EGF to increase CAMP accumulation was completely obliterated. TGF-P1 neither decreased immunoprecipitable EGF receptors in membranes from cardiomyocytes nor altered the specific binding of [ "'IIEGF to cardiomyocyte membranes. However, TGF-Pl decreased the ability of EGF to phosphorylate membrane proteins on tyrosine residues. TGF-Pl treatment of cardiomyocytes also decreased the ability of forskolin to augment CAMP accumulation in intact cells and stimulate adenylyl cyclase activity. Similarly, in membranes of TGF-P1 -treated cells, neither isoproterenol nor EGF stimulated adenylyl cyclase activity. Interestingly, as assessed by the ability of A1 F,to stimulate adenylyl cyclase, TGF-P1 did not alter the coupling between G, and catalytic subunits. Likewise, TGF-Pl did not alter the functional activity of the inhibitory regulatory element of the system, G,. Western analysis of cellular proteins revealed that TGF-P1 did not alter the amounts of G,,, G,,,, and G,, %. We conclude that TGF-P1 attenuates EGF-elicited CAMP accumulation in cardiomyocytes, in part, by decreasing the EGF receptor kinase function and that TGF-P1 -mt,diated alterations in the activity of adenylyl cyclase catalytic subunit also contribute toward the regulation of adenylyl cyclase by various agonists.