Guo H F, The I, Hannan F, Bernards A, Zhong Y
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Science. 1997 May 2;276(5313):795-8. doi: 10.1126/science.276.5313.795.
The human neurofibromatosis type 1 (NF1) tumor suppressor protein functions as a Ras-specific guanosine triphosphatase-activating protein, but the identity of Ras- mediated pathways modulated by NF1 remains unknown. A study of Drosophila NF1 mutants revealed that NF1 is essential for the cellular response to the neuropeptide PACAP38 (pituitary adenylyl cyclase-activating polypeptide) at the neuromuscular junction. The peptide induced a 100-fold enhancement of potassium currents by activating the Ras-Raf and adenylyl cyclase-adenosine 3',5'-monophosphate (cAMP) pathways. This response was eliminated in NF1 mutants. NF1 appears to regulate the rutabaga-encoded adenylyl cyclase rather than the Ras-Raf pathway. Moreover, the NF1 defect was rescued by the exposure of cells to pharmacological treatment that increased concentrations of cAMP.
人类1型神经纤维瘤病（NF1）肿瘤抑制蛋白作为一种Ras特异性鸟苷三磷酸酶激活蛋白发挥作用，但由NF1调节的Ras介导途径的身份仍然未知。一项对果蝇NF1突变体的研究表明，NF1对于神经肌肉接头处细胞对神经肽PACAP38（垂体腺苷酸环化酶激活多肽）的反应至关重要。该肽通过激活Ras-Raf和腺苷酸环化酶-3',5'-环磷酸腺苷（cAMP）途径使钾电流增强了100倍。这种反应在NF1突变体中消失。NF1似乎调节由rutabaga编码的腺苷酸环化酶，而不是Ras-Raf途径。此外，通过将细胞暴露于增加cAMP浓度的药物治疗中，NF1缺陷得以挽救。
