tailieunhanh - Báo cáo khoa học: ATP allosteric activation of atrial natriuretic factor receptor guanylate cyclase

Atrial natriuretic factor receptor guanylate cyclase (ANF-RGC) is the receptor and the signal transducer of two natriuretic peptide hormones: atrial natriuretic factor and brain natriuretic peptide. It is a single trans-membrane-spanning protein. It binds these hormones at its extracellular domain and activates its intracellular catalytic domain. | ATP allosteric activation of atrial natriuretic factor receptor guanylate cyclase Teresa Duda Prem Yadav and Rameshwar K. Sharma Research Divisions of Biochemistry and Molecular Biology The Unit of Regulatory and Molecular Biology Salus University Elkins Park PA USA Keywords allosteric regulation ANF receptor guanylate cyclase ATP membrane guanylate cyclase staurosporine Correspondence T. Duda Research Divisions of Biochemistry and Molecular Biology The Unit of Regulatory and Molecular Biology Salus University 8360 Old York Road Elkins Park PA 19027 USA Fax 1 215 780 315 Tel 1 215 780 3112 E-mail tduda@ Received 4 March 2010 revised 26 March 2010 accepted 1 April 2010 doi Atrial natriuretic factor receptor guanylate cyclase ANF-RGC is the receptor and the signal transducer of two natriuretic peptide hormones atrial natriuretic factor and brain natriuretic peptide. It is a single transmembrane-spanning protein. It binds these hormones at its extracellular domain and activates its intracellular catalytic domain. This results in the accelerated production of cyclic GMP a second messenger in controlling blood pressure cardiac vasculature and fluid secretion. ATP is obligatory for the transduction of this hormonal signal. Two models of ATP action have been proposed. In Model 1 it is a direct allosteric transducer. It binds to the defined regulatory domain ATP-regulated module juxtaposed to the C-terminal side of the transmembrane domain of ANF-RGC induces a cascade of temporal and spatial changes and activates the catalytic module residing at the C-terminus of the cyclase. In Model 2 before ATP can exhibit its allosteric effect ANF-RGC must first be phosphorylated by an as yet unidentified protein kinase. This initial step is obligatory in atrial natriuretic factor signaling of ANF-RGC. Until now none of these models has been directly validated because it has not been possible to segregate the allosteric and the phosphorylation