Xu H, Sweeney D, Greengard P, Gandy S
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4081-4. doi: 10.1073/pnas.93.9.4081.
Various compounds that affect signal transduction regulate the relative utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the production of nonamyloidogenic soluble beta APP (s beta APP) and decreasing that of amyloidogenic beta-amyloid peptide. In a recent study directed toward elucidating the mechanisms underlying phorbol ester-stimulated s beta APP secretion from cells, it was demonstrated that protein kinase C increases the formation from the trans-Golgi network (TGN) of beta APP-containing secretory vesicles. Here we present evidence that forskolin increases s beta APP production from intact PC12 cells, and protein kinase A stimulates formation from the TGN of beta APP-containing vesicles. Although protein kinase A and protein kinase C converge at the level of formation from the TGN of beta APP-containing vesicles, additional evidence indicates that the regulatory mechanisms involved are distinct.
多种影响信号转导的化合物可调节完整细胞中β-淀粉样前体蛋白（β-APP）替代加工途径的相对利用情况，增加非淀粉样生成性可溶性β-APP（sβ-APP）的产生，并减少淀粉样生成性β-淀粉样肽的产生。在最近一项旨在阐明佛波酯刺激细胞分泌sβ-APP的潜在机制的研究中，已证明蛋白激酶C可增加含β-APP分泌囊泡从反式高尔基体网络（TGN）的形成。在此我们提供证据表明，福司可林可增加完整PC12细胞中sβ-APP的产生，且蛋白激酶A可刺激含β-APP囊泡从TGN的形成。尽管蛋白激酶A和蛋白激酶C在含β-APP囊泡从TGN的形成水平上有共同作用，但其他证据表明所涉及的调节机制是不同的。
