Duda T, Goraczniak R M, Sharma R K
Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141.
FEBS Lett. 1993 Dec 13;335(3):309-14. doi: 10.1016/0014-5793(93)80408-m.
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. Obligatory in this activation process is an ATP-dependent step. ATP directly binds to a defined ATP-regulatory module (ARM) sequence motif in the cyclases and through ARM bridges the events of ligand binding and signal transduction. These ARM sequence motifs are respectively represented by Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509 and Gly499-Xa-Xa-Xa-Gly503 in the case of ANF receptor guanylate cyclase (ANF-RGC) and CNP receptor guanylate cyclase (CNP-RGC). Through genetic remodeling techniques, we now show that ARM-Gly505 in ANF-RGC and the corresponding ARM-Gly499 in CNP-RGC are critical for ANF and CNP signaling, and other ARM-Gly residues have minimal effect in the respective signaling processes.
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，兼具配体结合活性和催化活性。在这两种蛋白中，配体与细胞外受体结构域结合会激活胞质催化结构域，生成第二信使环磷酸鸟苷（cGMP）。此激活过程中必不可少的是一个ATP依赖步骤。ATP直接结合到环化酶中一个特定的ATP调节模块（ARM）序列基序上，并通过ARM将配体结合事件和信号转导联系起来。在心房利钠因子受体鸟苷酸环化酶（ANF-RGC）和C型利钠肽受体鸟苷酸环化酶（CNP-RGC）中，这些ARM序列基序分别由Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509和Gly499-Xa-Xa-Xa-Gly503表示。通过基因重塑技术，我们现在表明，ANF-RGC中的ARM-Gly505和CNP-RGC中的相应ARM-Gly499对ANF和CNP信号传导至关重要，而其他ARM-Gly残基在各自的信号传导过程中影响极小。
