Amyloid β Protein Precursor Is Phosphorylated by JNK-1 Independent of, yet Facilitated by, JNK-Interacting Protein (JIP)-1

• Published in: The Journal of biological chemistry Vol. 278; no. 43; p. 42058
• Main Authors: Meir H. Scheinfeld, Enrico Ghersi, Peter Davies, Luciano D'Adamio
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 24.10.2003
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M304853200

Alzheimer's disease (AD) is genetically linked to the processing of amyloid β protein precursor (AβPP). Aside from being the precursor of the amyloid β (Aβ) found in plaques in the brains of patients with AD, little is known regarding the functional role of AβPP. We have recently reported biochemical evidence linking AβPP to the JNK signaling cascade by finding that JNK-interacting protein-1 (JIP-1) binds AβPP. In order to study the functional implications of this interaction we assayed the carboxyl-terminal of AβPP for phosphorylation. We found that the threonine 668 within the AβPP intracellular domain (AID or elsewhere AICD) is indeed phosphorylated by JNK1. We surprisingly found that although JIP-1 can facilitate this phosphorylation, it is not required for this process. We also found that JIP-1 only facilitated phosphorylation of AβPP but not of the two other family members APLP1 (amyloid precursor-like protein 1) and APLP2. Understanding the connection between AβPP phosphorylation and the JNK signaling pathway, which mediates cell response to stress may have important implications in understanding the pathogenesis of Alzheimer's disease.