Singh S, Lowe D G, Thorpe D S, Rodriguez H, Kuang W J, Dangott L J, Chinkers M, Goeddel D V, Garbers D L
Department of Pharmacology, Vanderbilt Medical Center, Nashville, Tennessee 37232.
Nature. 1988 Aug 25;334(6184):708-12. doi: 10.1038/334708a0.
Guanylate cyclase has been strongly implicated as a cell-surface receptor on spermatozoa for a chemotactic peptide, and on various other cells as a receptor for atrial natriuretic peptides. Resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2), the chemotactic peptide released by sea urchin Arbacia punctulata eggs, is specifically crosslinked to A. punctulata spermatozoan guanylate cyclase. After the binding of the peptide the state of guanylate cyclase phosphorylation modulates enzyme activity. We report here that the deduced amino-acid sequence of the spermatozoan membrane form of guanylate cyclase predicts an intrinsic membrane protein of 986 amino acids with an amino-terminal signal sequence. A single transmembrane domain separates the protein into putative extracellular and cytoplasmic-catalytic domains. The cytoplasmic carboxyl-terminal 95 amino acids contain 20% serine, the likely regulatory sites for phosphorylation. Unexpectedly, the enzyme is homologous to the protein kinase family.
鸟苷酸环化酶被强烈认为是精子表面趋化肽的受体，在其他各种细胞中则是心钠素的受体。海胆 punctulata 卵释放的趋化肽 Resact（半胱氨酸 - 缬氨酸 - 苏氨酸 - 甘氨酸 - 丙氨酸 - 脯氨酸 - 甘氨酸 - 半胱氨酸 - 缬氨酸 - 甘氨酸 - 甘氨酸 - 甘氨酸 - 精氨酸 - 亮氨酸 - 氨基）能特异性地与 punctulata 精子鸟苷酸环化酶交联。肽结合后，鸟苷酸环化酶的磷酸化状态会调节酶的活性。我们在此报告，精子膜形式的鸟苷酸环化酶推导的氨基酸序列预测其为一个含 986 个氨基酸的内在膜蛋白，带有氨基末端信号序列。一个单一的跨膜结构域将该蛋白分为假定的细胞外和细胞质催化结构域。细胞质羧基末端的 95 个氨基酸中 20%为丝氨酸，这可能是磷酸化的调节位点。出乎意料的是，该酶与蛋白激酶家族同源。
