Abstract
In familial Alzheimer's disease (FAD), mutations to I, F, and G have been discovered at V642 in the neuron‐specific version of the amyloid precursor protein APP695. It has been found that expression of each FAD mutant suppresses the transcriptional activity of the cAMP response element CRE in a Gαo‐dependent manner in a COS cell clone NK1 [Ikezu et al. (1996) EMBO J. 15, 2468–2475]. Here we show that adenylyl cyclase (AC) inhibition is probably not the prerequisite for this pathway. First, expression of each FAD mutant in NK1 cells had no effect on AC activity stimulated by cholera toxin and by mutationally activated Gαs, although the same expression completely repressed the stimulated CRE. Second, a transfected activating mutant of Gαo inhibited CRE without detectable suppression of AC, whereas similarly transfected activating Gαi2 inhibited both AC and CRE. Third, FAD mutant‐induced inhibition occurred for CRE activity stimulated by dibutyryl cAMP. These data suggest that CRE suppression by FAD mutants of APP could occur independently of AC.
References
34
Referenced
8
10.1038/ng0792-233
10.1212/WNL.42.8.1445
10.1038/373523a0
10.1002/j.1460-2075.1996.tb00750.x
10.1074/jbc.270.52.30853
10.1074/jbc.271.37.22782
10.1038/362075a0
10.1002/j.1460-2075.1995.tb00033.x
10.1073/pnas.85.10.3638
10.1038/344836a0
10.1523/JNEUROSCI.13-07-03112.1993
10.1006/excr.1995.1339
10.1074/jbc.270.9.4205
10.1159/000213818
10.1002/j.1460-2075.1996.tb00604.x
10.1016/0092-8674(94)90400-6
10.1016/0092-8674(94)90399-9
10.1016/0092-8674(94)90394-8
10.1016/S0021-9258(18)31788-5
10.1002/j.1460-2075.1996.tb00382.x
10.1074/jbc.270.49.29224
10.1073/pnas.90.24.11772
10.1016/0092-8674(89)90013-5
10.1126/science.2116665
-
Wong Y.H. Federman A. Pace A.M. Zachary I. Evans T. Pouysségur J. and Bourne H.R. (1991) Nature 351 63–65.
(
10.1038/351063a0
) 10.1016/S0021-9258(19)62023-5
10.1016/S0014-5793(97)00257-3
10.1038/333129a0
10.1128/MCB.14.9.6107
10.1101/gad.8.21.2527
10.1126/science.1378648
10.1073/pnas.92.24.11175
10.1126/science.1321493
10.1016/0304-3940(93)90592-9
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 25, 2002, 8:19 a.m.) |
Deposited | 1 year, 11 months ago (Sept. 15, 2023, 11:45 p.m.) |
Indexed | 1 month, 1 week ago (July 25, 2025, 6:53 a.m.) |
Issued | 28 years, 1 month ago (July 21, 1997) |
Published | 28 years, 1 month ago (July 21, 1997) |
Published Online | 27 years, 10 months ago (Nov. 3, 1997) |
Published Print | 28 years, 1 month ago (July 21, 1997) |
@article{Giambarella_1997, title={Potential CRE suppression by familial Alzheimer’s mutants of APP independent of adenylyl cyclase regulation}, volume={412}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/s0014-5793(97)00753-9}, DOI={10.1016/s0014-5793(97)00753-9}, number={1}, journal={FEBS Letters}, publisher={Wiley}, author={Giambarella, Ugo and Murayama, Yoshitake and Ikezu, Tsuneya and Fujita, Toshiro and Nishimoto, Ikuo}, year={1997}, month=jul, pages={97–101} }