CORE SEQUENCE OF ATP REGULATORY MODULE IN RECEPTOR GUANYLATE CYCLASES
CORE SEQUENCE OF ATP REGULATORY MODULE IN RECEPTOR GUANYLATE CYCLASES
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DOI：
10.1016/0014-5793(93)81151-o
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发表时间：
1993-01-04
期刊：
影响因子：
3.5
通讯作者：
SHARMA, RK
中科院分区：
文献类型：
--
作者：
DUDA, T;GORACZNIAK, RM;SHARMA, RK
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，具有配体结合和催化活性。在这两种蛋白质中，配体与细胞外受体结构域结合激活胞质催化结构域，产生第二信使环GMP。ANF受体鸟苷酸环化酶（ANF-RGC）的研究表明，在这个激活过程中，强制性的是ATP依赖的步骤。ATP直接与环化酶结合并桥接配体结合和信号转导事件。环化酶中的一个确定的ATP调节模块（ARM）序列（Gly 503-Arg-Gly-Ser-Asn-Tyr-Gly 509）在ATP介导的事件中至关重要。通过遗传重塑技术，我们现在已经确定了核心ARM序列，这是必不可少的ANF和CNP信号。该序列为Gly-Xa-Xa-Xa-Gly，在ANF-RGC ARM的情况下由Gly 505-Ser-Asn-Tyr-Gly 509表示，在CNP受体鸟苷酸环化酶ARM中由Gly 499-Ser-Ser-Tyr-Gly 503表示。
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.