Duda T, Goraczniak R M, Sharma R K
Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141.
FEBS Lett. 1993 Jan 4;315(2):143-8. doi: 10.1016/0014-5793(93)81151-o.
Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP)-activated guanylate cyclases are single-chain transmembrane-spanning proteins, containing both ligand binding and catalytic activities. In both proteins, ligand binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Studies with ANF receptor guanylate cyclase (ANF-RGC) have indicated that obligatory in this activation process is an ATP-dependent step. ATP directly binds to the cyclase and bridges the events of ligand binding and signal transduction. A defined ATP-regulated module (ARM) sequence (Gly503-Arg-Gly-Ser-Asn-Tyr-Gly509) in the cyclase is critical in the ATP-mediated event. Through genetic remodeling techniques, we have now identified the core ARM sequence that is essential in both ANF and CNP signaling. This sequence is Gly-Xa-Xa-Xa-Gly, represented by Gly505-Ser-Asn-Tyr-Gly509 in the case of ANF-RGC ARM and by Gly499-Ser-Ser-Tyr-Gly503 in the CNP receptor guanylate cyclase ARM.
心房利钠因子（ANF）和C型利钠肽（CNP）激活的鸟苷酸环化酶是单链跨膜蛋白，兼具配体结合和催化活性。在这两种蛋白中，配体与细胞外受体结构域的结合会激活胞质催化结构域，生成第二信使环磷酸鸟苷（cGMP）。对ANF受体鸟苷酸环化酶（ANF-RGC）的研究表明，这一激活过程中必不可少的是一个依赖ATP的步骤。ATP直接与环化酶结合，并在配体结合和信号转导事件之间起桥梁作用。环化酶中一个特定的ATP调节模块（ARM）序列（Gly503-Arg-Gly-Ser-Asn-Tyr-Gly509）在ATP介导的事件中至关重要。通过基因重塑技术，我们现已确定了在ANF和CNP信号传导中都必不可少的核心ARM序列。该序列为Gly-Xa-Xa-Xa-Gly，在ANF-RGC的ARM中由Gly505-Ser-Asn-Tyr-Gly509代表，在CNP受体鸟苷酸环化酶的ARM中由Gly499-Ser-Ser-Tyr-Gly503代表。
