Abstract：
Receptor guanylyl cyclases (GCs) are single membrane spanning, multidomain enzymes, that synthesize cGMP in response to natriuretic peptides or other ligands. They are evolutionarily conserved from sea urchins to humans and regulate diverse physiologies. Most family members are phosphorylated on four to seven conserved serines or threonines at the beginning of their kinase homology domains. This review describes studies that demonstrate that phosphorylation and dephosphorylation are required for activation and inactivation of these enzymes, respectively. Phosphorylation sites in GC-A, GC-B, GC-E and sea urchin receptors are discussed as are mutant receptors that mimic the dephosphorylated, inactive or phosphorylated, active forms of GC-A and GC-B, respectively. A salt bridge model is described that explains why phosphorylation is required for enzyme activation. Potential kinases, phosphatases and ATP regulation of GC receptors are also discussed. Critically, knock-in mice with glutamate substitutions for receptor phosphorylation sites are described. The inability of opposing signaling pathways to inhibit cGMP synthesis in mice where GC-A or GC-B cannot be dephosphorylated demonstrates the necessity of receptor dephosphorylation in vivo. Cardiac hypertrophy, oocyte meiosis, long bone growth/achondroplasia, and bone density are regulated by GC phosphorylation, but additional processes are likely to be identified in the future.
摘要：
受体鸟苷酸环化酶（GC）是跨膜的，多域酶，响应利钠肽或其他配体合成cGMP。它们在进化上从海胆到人类是保守的，并调节各种生理。大多数家族成员在其激酶同源结构域开始时在4至7个保守丝氨酸或苏氨酸上被磷酸化。这篇综述描述了一些研究，这些研究表明磷酸化和去磷酸化是激活和失活这些酶所必需的。分别。GC-A中的磷酸化位点，GC-B,讨论了GC-E和海胆受体以及模拟去磷酸化的突变受体，无活性或磷酸化，GC-A和GC-B的活性形式，分别。描述了盐桥模型，该模型解释了为什么酶激活需要磷酸化。潜在激酶，还讨论了GC受体的磷酸酶和ATP调节。严重的,描述了具有受体磷酸化位点的谷氨酸替换的敲入小鼠。在GC-A或GC-B不能去磷酸化的小鼠中，相反的信号传导途径不能抑制cGMP合成，这表明了体内受体去磷酸化的必要性。心脏肥大,卵母细胞减数分裂,长骨生长/软骨发育不全，骨密度受GC磷酸化调节，但是将来可能会发现其他过程。
