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首页> 外文期刊>Biochemistry >Phosphorylation-dependent regulation of the guanylyl cyclase-linked natriuretic peptide receptor B: Dephosphorylation is a mechanism of desensitization
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Phosphorylation-dependent regulation of the guanylyl cyclase-linked natriuretic peptide receptor B: Dephosphorylation is a mechanism of desensitization

机译：鸟苷酸环化酶连接的利钠肽受体B的磷酸化依赖性调节：去磷酸化是脱敏机制

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摘要

C-type natriuretic peptide (CNP) binds the guanylyl cyclase-linked natriuretic peptide receptor B (NPR-B) and stimulates marked elevations of the intracellular signaling molecule, cGMP. Here, the essential role of phosphorylation in the hormonal activation and deactivation of this receptor is described. Exposure of NIH3T3 fibroblasts overexpressing NPR-B (3T3-NPR-B) to CNP resulted in time-dependent decreases in both subsequent CNP-dependent cGMP elevations in whole cells and hormone-dependent guanylyl cyclase activity assayed in crude membranes, NPR-B isolated from resting 3T3-NPR-B cells was phosphorylated on serine and threonine residues, and exposure to CNP resulted in a time-dependent dephosphorylation and desensitization of the receptor. Immunoblot analysis and guanylyl cyclase activity assayed with the general activators Mn2+ and Triton X-100 indicated that these reductions were not due to receptor degradation. Tryptic phosphopeptide mapping analysis suggested that CNP treatment caused a complete dephosphorylation of approximately one-half of the NPR-B population. In vitro dephosphorylation of crude 3T3-NPR-B membranes with purified protein phosphatase 2A was highly correlated with losses in CNP-but not Mn2+- and Triton X-100-dependent guanylyl cyclase activity. Taken together, these data indicate that the catalytic activity of NPR-B is tightly coupled to its phosphorylation state and that dephosphorylation is a mechanism of desensitization. [References: 47]
机译：C型利钠肽（CNP）与鸟苷酸环化酶连接的利钠肽受体B（NPR-B）结合，并刺激细胞内信号分子cGMP明显升高。在此，描述了磷酸化在该受体的激素激活和失活中的重要作用。将过表达NPR-B（3T3-NPR-B）的NIH3T3成纤维细胞暴露于CNP会导致全细胞后续CNP依赖性cGMP升高的时间依赖性下降以及粗膜中测定的激素依赖性鸟苷酸环化酶活性来自静止的3T3-NPR-B细胞的丝氨酸和苏氨酸残基被磷酸化，暴露于CNP导致受体的时间依赖性去磷酸化和脱敏。使用通用激活剂Mn2 +和Triton X-100进行的免疫印迹分析和鸟苷酰环化酶活性表明，这些减少并不是由于受体降解引起的。胰蛋白酶磷酸肽图分析表明，CNP处理导致大约一半的NPR-B人口完全脱磷酸。粗3T3-NPR-B膜与纯化的蛋白磷酸酶2A的体外去磷酸化与CNP的损失高度相关，但与Mn2 +和Triton X-100依赖的鸟苷酸环化酶活性没有损失。总而言之，这些数据表明NPR-B的催化活性与其磷酸化状态紧密相关，并且脱磷酸化是脱敏的机制。 [参考：47]

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