Phosphorylation of LRP1 regulates the interaction with Fe65

作者：Klug Wilfried; Dietl Andreas; Simon Bernd; Sinning Irmgard; Wild Klemens^*

来源：FEBS Letters, 2011, 585(20): 3229-3235.

DOI：10.1016/j.febslet.2011.09.028

• Fe65
• LDL receptor-related protein 1 (LRP1)
• Phosphotyrosine binding domain (PTB)
• NPXY
• Phosphorylation
• Amyloid precursor protein (APP)

Neuronal Fe65 is a central adapter for the intracellular protein network of Alzheimer's disease related amyloid precursor protein (APP). It contains a unique tandem array of phosphotyrosine-binding (PTB) domains that recognize NPXY internalization motifs present in the intracellular domains of APP (AICD) and the low-density lipoprotein receptor-related protein LRP1 (LICD). The ternary APP/Fe65/LRP1 complex is an important mediator of APP processing and affects beta-amyloid peptide production. Here we dissect by biochemical and biophysical methods the direct interactions within the ternary complex and reveal a phosphorylation-dependent insulin receptor substrate (IRS-) like interaction of the distal NPVY(4507) motif of LICD with Fe65-PTB1.
Structured summary of protein interactions:
APP-AICD and FE65 bind by nuclear magnetic resonance (View interaction)
Src phosphorylates LRP1-LICD by protein kinase assay (View interaction)
LRP1-LICD physically interacts with FE65 and APP-AICD by pull down (View interaction)
FE65-PTB1 and LRP1-LICD bind by nuclear magnetic resonance (View interaction)
LRP1-LICD binds to FE65-PTB1 by pu