Distinct inhibitory ATP-regulated modulatory domain (ARMi) in membrane guanylate cyclases.
Distinct inhibitory ATP-regulated modulatory domain (ARMi) in membrane guanylate cyclases.
复制标题
膜鸟苷酸环化酶中独特的抑制性 ATP 调节调节域 (ARMi)。
DOI：
10.1042/bj3190279
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Sharma,RK
中科院分区：
文献类型：
--
作者：
Duda,T;Goraczniak,R;Sharma,RK
根据辅助因子Mg 2+或Mn 2+，ATP刺激或抑制利钠因子受体鸟苷酸环化酶、ANF-RGC和CNP-RGC的信号转导活性：在Mg 2+存在下存在刺激，在Mn 2+存在下存在抑制。一个明确的核心ATP调节的调节（ARM）序列基序内的细胞内的“激酶样”结构域的环化酶的刺激是至关重要的，但抑制性转导过程的机制是未知的。此外，ATP抑制视杆细胞外节膜鸟苷酸环化酶（ROS-GC）的基础环化酶活性。这种抑制性转导过程的机制也是未知的。这些问题已在本调查中通过删除突变/表达的环化酶的研究计划得到解决。研究表明，ATP介导的利钠因子受体环化酶和ROS-GC的抑制性转导过程是相同的。所有这些环化酶的ATP调节的抑制结构域都位于环化酶的C-末端区段内。该结构域位于与代表ATP刺激ARM.C-末端片段中抑制性结构域的鉴定不同的位置，表明该片段由两个独立的结构域组成：一个代表催化性环化酶结构域，另一个代表ATP调节抑制性（ARMi）结构域。这些研究结果建立了一个新的ATP介导的抑制性转导机制的膜鸟苷酸环化酶，这是不同的，它的对应物，刺激ATP介导的激素信号转导机制。因此，他们定义了一个新的范例鸟苷酸环化酶连接的信号转导途径。
Depending upon the cofactors Mg2+or Mn2+, ATP stimulates or inhibits the signal transduction activities of the natriuretic factor receptor guanylate cyclases, ANF-RGC and CNP-RGC: there is stimulation in the presence of Mg2+and inhibition in the presence of Mn2+. A defined core ATP-regulated modulatory (ARM) sequence motif within the intracellular ‘kinase-like’ domain of the cyclases is critical for stimulation, but the mechanism of the inhibitory transduction process is not known. In addition, ATP inhibits the basal cyclase activity of a rod outer segment membrane guanylate cyclase (ROS-GC). The mechanism of this inhibitory transduction process is also not known. These issues have been addressed in the present investigation through a program of deletion mutagenesis/expression studies of the cyclases. The study shows that the ATP-mediated inhibitory transduction processes of the natriuretic factor receptor cyclases and of ROS-GC are identical. The ATP-regulated inhibitory domain of all these cyclases resides within the C-terminal segment of the cyclase. This domain is in a different location from the one representing the ATP-stimulatory ARM. The identification of the inhibitory domain in the C-terminal segment of the cyclase indicates that this segment is composed of two separate domains: one representing a catalytic cyclase domain and the other an ATP-regulated inhibitory (ARMi) domain. These findings establish a novel ATP-mediated inhibitory transduction mechanism of the membrane guanylate cyclases which is distinct from that of its counterpart, the stimulatory ATP-mediated hormonal signal transduction mechanism. Thus, they define a new paradigm of guanylate cyclase-linked signal transduction pathways.