Cyclophilin A Functions as an Endogenous Inhibitor for Membrane-Bound Guanylate Cyclase-A

• DOI: 10.1161/01.hyp.0000145859.94894.23
• Publication Date: 2004-10-05T00:14:53Z
• Authors: Zi-Jiang Chen; Michael Vetter; Geen-Dong Chang; Shiguo Liu; Danian Che; Yaxian Ding; Sung Soo Kim; Chung-Ho Chang
• Keywords: Cypa; Cis-trans-Isomerases

Cyclophilin A (CypA), a receptor for the immunosuppressive agent cyclosporin A, is cis-trans-peptidyl-prolyl isomerase (PPIase). It accelerates cis-trans isomerization of prolyl-peptide bonds. CypA binds and regulates activity variety proteins. Atrial natriuretic factor (ANF) its membrane-bound guanylate cyclase-A (GC-A) are involved in regulation blood pressure. We examined whether affects activation GC-A by ANF. The results showed that associated with GC-A. Interestingly, binding ANF to released CypA. Transfection inhibited ANF-stimulated activity, indicating functions as an endogenous inhibitor activation. also inhibits cyclase-C (GC-c), catalytic domain GC-A, interacts In contrast, transfection R55A, mutant expressing low PPIase did not significantly attenuate GC-c Inhibition blocks inhibitory effect on activity. These demonstrate required inhibit Furthermore, mutation Pro 822, 902, or 958 abolished Therefore, it likely catalyzes 958, which keeps inactive state, alters conformation releases from leading enzyme