TY - JOUR
T1 - Tyrosine phosphorylation of the β-amyloid precursor protein cytoplasmic tail promotes interaction with Shc
AU - Tarr, Philip E.
AU - Roncarati, Roberta
AU - Pelicci, Giuliana
AU - Pelicci, Pier Giuseppe
AU - D'Adamio, Luciano
PY - 2002/5/10
Y1 - 2002/5/10
N2 - β-Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease. The cytoplasmic tail of APP interacts with phosphotyrosine binding (PTB) domain containing proteins (Fe65, X11, mDab-1, and JIP-1) and may modulate gene expression and apoptosis. We now identify Shc A and Shc C, PTB-containing adapter proteins that signal to cellular differentiation and survival pathways, as novel APP-interacting proteins. The APP cytoplasmic tail contains a PTB-binding motif (Y682ENPTY687) that, when phosphorylated on Tyr682, precipitated the PTB domain of Shc A and Shc C, as well as endogenous full-length Shc A. APP and Shc C were physically associated in adult mouse brain homogenates. Increase in phosphorylation of APP by overexpression of the nerve growth factor receptor Trk A in 293T cells promoted the interaction of transfected APP and endogenous Shc A. Pervanadate treatment of N2a neuroblastoma cells resulted in tyrosine phosphorylation and association of endogenous APP and Shc A. Thus, APP and Shc proteins interact in vitro, in cells, and in the mouse brain. Tyrosine phosphorylation of APP may promote the interaction with Shc proteins.
AB - β-Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease. The cytoplasmic tail of APP interacts with phosphotyrosine binding (PTB) domain containing proteins (Fe65, X11, mDab-1, and JIP-1) and may modulate gene expression and apoptosis. We now identify Shc A and Shc C, PTB-containing adapter proteins that signal to cellular differentiation and survival pathways, as novel APP-interacting proteins. The APP cytoplasmic tail contains a PTB-binding motif (Y682ENPTY687) that, when phosphorylated on Tyr682, precipitated the PTB domain of Shc A and Shc C, as well as endogenous full-length Shc A. APP and Shc C were physically associated in adult mouse brain homogenates. Increase in phosphorylation of APP by overexpression of the nerve growth factor receptor Trk A in 293T cells promoted the interaction of transfected APP and endogenous Shc A. Pervanadate treatment of N2a neuroblastoma cells resulted in tyrosine phosphorylation and association of endogenous APP and Shc A. Thus, APP and Shc proteins interact in vitro, in cells, and in the mouse brain. Tyrosine phosphorylation of APP may promote the interaction with Shc proteins.
UR - http://www.scopus.com/inward/record.url?scp=0037053281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037053281&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110286200
DO - 10.1074/jbc.M110286200
M3 - Article
C2 - 11877420
AN - SCOPUS:0037053281
SN - 0021-9258
VL - 277
SP - 16798
EP - 16804
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 19
ER -