Schulz S, Green C K, Yuen P S, Garbers D L
Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Cell. 1990 Nov 30;63(5):941-8. doi: 10.1016/0092-8674(90)90497-3.
Plasma membrane forms of guanylyl cyclase have been shown to function as natriuretic peptide receptors. We describe a new clone (GC-C) encoding a guanylyl cyclase receptor for heat-stable enterotoxin. GC-C encodes a protein containing an extracellular amino acid sequence divergent from that of previously cloned guanylyl cyclases; however, the protein retains the intracellular protein kinase-like and cyclase catalytic domains. Expression of GC-C in COS-7 cells results in high guanylyl cyclase activity. In addition, heat-stable enterotoxin from E. coli, but not natriuretic peptides, causes marked elevations of cyclic GMP and is specifically bound by cells transfected with GC-C. The enterotoxin fails to elevate cyclic GMP in nontransfected cells or in cells transfected with the natriuretic peptide/guanylyl cyclase receptors. These results show that a heat-stable enterotoxin receptor responsible for acute diarrhea is a plasma membrane form of guanylyl cyclase.
已证明鸟苷酸环化酶的质膜形式可作为利钠肽受体发挥作用。我们描述了一种新的克隆体（GC-C），它编码一种热稳定肠毒素的鸟苷酸环化酶受体。GC-C编码的蛋白质含有一段与先前克隆的鸟苷酸环化酶不同的细胞外氨基酸序列；然而，该蛋白质保留了细胞内蛋白激酶样结构域和环化酶催化结构域。GC-C在COS-7细胞中的表达导致鸟苷酸环化酶活性升高。此外，来自大肠杆菌的热稳定肠毒素而非利钠肽会导致环磷酸鸟苷显著升高，并被转染了GC-C的细胞特异性结合。该肠毒素在未转染的细胞或转染了利钠肽/鸟苷酸环化酶受体的细胞中不会使环磷酸鸟苷升高。这些结果表明，负责急性腹泻的热稳定肠毒素受体是鸟苷酸环化酶的质膜形式。
