Duda T, Goraczniak R M, Sharma R K
Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141, USA.
Biochem Biophys Res Commun. 1995 Jul 26;212(3):1046-53. doi: 10.1006/bbrc.1995.2075.
The type A (ANF) and the type C (CNP) natriuretic factor-activated guanylate cyclases, respectively termed as ANF-RGC and CNP-RGC, are single-chain transmembrane-spanning proteins, containing ligand binding and catalytic cyclase domains at two opposite ends of the protein. The binding activity resides at the N-terminal extracellular region and the catalytic cyclase activity at the carboxyl end. The ANF-RGC residue Leu-364, residing in the extracellular region, is critical for the ANF-binding activity; the CNP-RGC residue Glu-332 is critical for the CNP-binding activity. The counter part of CNP-RGC-Glu-332 residue is the ANF-RGC residue Gln-338 and of ANF-RGC-Leu-364 residue in CNP-RGC is the Valine-358. The present study shows a remarkable signal switching phenomenon associated with these residues. By changing the ANF-RGC residue Gln-338 to Glu, ANF-RGC switches from no to significant CNP signal transduction activity; similarly, a change from Valine-358 to Leu generates ANF signal transduction activity in CNP-RGC. These acquired signal transduction activities in the cyclases are in addition to their natural signal transduction activities. Thus, these new cyclases show both ANF and CNP signaling activities.
A型（ANF）和C型（CNP）利钠肽激活的鸟苷酸环化酶，分别称为ANF-RGC和CNP-RGC，是单链跨膜蛋白，在蛋白质的两端分别含有配体结合域和催化环化酶结构域。结合活性位于N端细胞外区域，催化环化酶活性位于羧基端。位于细胞外区域的ANF-RGC残基Leu-364对ANF结合活性至关重要；CNP-RGC残基Glu-332对CNP结合活性至关重要。CNP-RGC-Glu-332残基的对应部分是ANF-RGC残基Gln-338，而CNP-RGC中ANF-RGC-Leu-364残基的对应部分是缬氨酸-358。本研究显示了与这些残基相关的显著信号转换现象。通过将ANF-RGC残基Gln-338变为Glu，ANF-RGC从无CNP信号转导活性转变为有显著的CNP信号转导活性；同样，将缬氨酸-358变为Leu会在CNP-RGC中产生ANF信号转导活性。环化酶中这些获得的信号转导活性是除其天然信号转导活性之外的。因此，这些新的环化酶同时显示出ANF和CNP信号活性。
