We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Results: 2

1.
FIGURE 1.

FIGURE 1. From: Regulation of Amyloid ?-Protein Precursor by Phosphorylation and Protein Interactions.

Phosphorylation of APP and APP CTFs in mouse brain. Upper panels, APP phosphorylation state in brain, primary cultured neurons, and glial cells. Lysates of brain (left), primary cultured cortical neurons (middle), and glial cells (right) were subjected to immunoprecipitation with an anti-pan-C-terminal APP antibody. The immunoprecipitates were analyzed by Western blotting using anti-pan-C-terminal APP (APP) and anti-phospho-Thr668 APP (pAPP) antibodies. The APP695 isoform was detected in the samples from brain and primary cultured neurons, whereas APP770 and APP751 were the major isoforms detected in the sample from primary cultured glial cells. Lower panels, APP CTFs and their phosphorylation state in brain. Brain lysates were immunoprecipitated with an anti-pan-C-terminal APP antibody and treated with (+) or without (–) λ-phosphatase. The samples were analyzed by Western blotting using an anti-pan-C-terminal APP (APP) antibody. C99 and C89 are CTFβ and CTFβ′, and C83 is CTFα. C50 and C51 are CTFγ/ε (AICD). pC99, pC89, pC83, pC50, and pC51 are CTFs phosphorylated at Thr668. Numbers indicate molecular size markers (in kilodaltons).

Toshiharu Suzuki, et al. J Biol Chem. 2008 October 31;283(44):29633-29637.
2.
FIGURE 2.

FIGURE 2. From: Regulation of Amyloid ?-Protein Precursor by Phosphorylation and Protein Interactions.

Amino acid sequence of the APP cytoplasmic region, functional motifs, and APP-binding partners. A, amino acid sequence of the APP cytoplasmic region. Numbers indicate amino acid positions of the APP695 isoform. Two functional motifs, 667VTPEER672 and 681GYENPTY687, are indicated. The Thr668 phosphorylation site is indicated (P). B, relationship between Thr668 phosphorylation in the 667VTPEER672 and 681GYENPTY687 motifs and interaction of APP-binding partners with the 681GYENPTY687 motif. Panel (i), the APP cytoplasmic region is characterized by the 667VTPEER672 turn as a helix-capping box structure, which stabilizes the helical structure of its C terminus, which contains the 681GYENPTY687 motif (28). Major APP-binding partners such as X11L, FE65, and JIP1b interact with the 681GYENPTY687 motif. Panel (ii), phosphorylation at Thr668 within the 667VTPEER672 motif induces structural change in the cytoplasmic region, releasing FE65 from the 681GYENPTY687 motif (29, 30). Panel (iii), binding of X11L to the 681GYENPTY687 motif may affect the structure of the 667VTPEER672 motif and expose Thr668, facilitating its phosphorylation by protein kinases such as JNK (45). Thus, phosphorylation of Thr668 acts as molecular switch to induce conformational change in the cytoplasmic region and to regulate protein interactions. TM, transmembrane domain.

Toshiharu Suzuki, et al. J Biol Chem. 2008 October 31;283(44):29633-29637.

Supplemental Content

Recent activity

Your browsing activity is temporarily unavailable.

Write to the Help Desk