Abstract
The phosphorylation of Tyr-682 residue in the intracellular domain (AID) of amyloid-β protein precursor (AβPP) is significantly enhanced in Alzheimer's disease patients' brain. The role of this phosphotyrosine, however, remains elusive. Here we report that phosphorylation of Tyr-682 inhibits the interactions between AβPP and Fe65, which is the main regulatory mechanism controlling Fe65 nuclear signaling. Furthermore, we show that tyrosine phosphorylation of AβPP also inhibits interaction of the two other Fe65 family members, Fe65L1 and Fe65L2. Likewise, docking of Fe65, Fe65L1 and Fe65L2 to APLP1 and APLP2, the two other members of the AβPP-gene family, is abolished by analogous phosphorylation events. Our results indicate that phosphorylation of the cytoplasmic tail of AβPP on Tyr-682 represents a second mechanism, alternative to AβPP processing by secretases, that regulates AβPP/Fe65 downstream signaling pathways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 301-307 |
| Number of pages | 7 |
| Journal | Journal of Alzheimer's Disease |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2009 |
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Keywords
- Amyloid-β protein precursor
- Fe65
- Phosphorylation
- Threonine
- Tyrosine
ASJC Scopus subject areas
- Psychiatry and Mental health
- Geriatrics and Gerontology
- Clinical Psychology
Cite this
Phosphorylation of a tyrosine in the amyloid-β protein precursor intracellular domain inhibits Fe65 binding and signaling. / Zhou, Dawang; Zambrano, Nicola; Russo, Tommaso; D'Adamio, Luciano.
In: Journal of Alzheimer's Disease, Vol. 16, No. 2, 2009, p. 301-307.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phosphorylation of a tyrosine in the amyloid-β protein precursor intracellular domain inhibits Fe65 binding and signaling
AU - Zhou, Dawang
AU - Zambrano, Nicola
AU - Russo, Tommaso
AU - D'Adamio, Luciano
PY - 2009
Y1 - 2009
N2 - The phosphorylation of Tyr-682 residue in the intracellular domain (AID) of amyloid-β protein precursor (AβPP) is significantly enhanced in Alzheimer's disease patients' brain. The role of this phosphotyrosine, however, remains elusive. Here we report that phosphorylation of Tyr-682 inhibits the interactions between AβPP and Fe65, which is the main regulatory mechanism controlling Fe65 nuclear signaling. Furthermore, we show that tyrosine phosphorylation of AβPP also inhibits interaction of the two other Fe65 family members, Fe65L1 and Fe65L2. Likewise, docking of Fe65, Fe65L1 and Fe65L2 to APLP1 and APLP2, the two other members of the AβPP-gene family, is abolished by analogous phosphorylation events. Our results indicate that phosphorylation of the cytoplasmic tail of AβPP on Tyr-682 represents a second mechanism, alternative to AβPP processing by secretases, that regulates AβPP/Fe65 downstream signaling pathways.
AB - The phosphorylation of Tyr-682 residue in the intracellular domain (AID) of amyloid-β protein precursor (AβPP) is significantly enhanced in Alzheimer's disease patients' brain. The role of this phosphotyrosine, however, remains elusive. Here we report that phosphorylation of Tyr-682 inhibits the interactions between AβPP and Fe65, which is the main regulatory mechanism controlling Fe65 nuclear signaling. Furthermore, we show that tyrosine phosphorylation of AβPP also inhibits interaction of the two other Fe65 family members, Fe65L1 and Fe65L2. Likewise, docking of Fe65, Fe65L1 and Fe65L2 to APLP1 and APLP2, the two other members of the AβPP-gene family, is abolished by analogous phosphorylation events. Our results indicate that phosphorylation of the cytoplasmic tail of AβPP on Tyr-682 represents a second mechanism, alternative to AβPP processing by secretases, that regulates AβPP/Fe65 downstream signaling pathways.
KW - Amyloid-β protein precursor
KW - Fe65
KW - Phosphorylation
KW - Threonine
KW - Tyrosine
UR - http://www.scopus.com/inward/record.url?scp=60349103104&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60349103104&partnerID=8YFLogxK
U2 - 10.3233/JAD-2009-0970
DO - 10.3233/JAD-2009-0970
M3 - Article
C2 - 19221419
AN - SCOPUS:60349103104
VL - 16
SP - 301
EP - 307
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 2
ER -