Abstract: Amyloid beta protein precursor is phosphorylated by JNK-1 independent of, yet facilitated by, JNK interacting protein (JIP)-1

J Biol Chem. 2003 Aug 13 [Epub ahead of print].

Scheinfeld MH, Ghersi E, Davies P, D’Adamio L.

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.

Alzheimer’s Disease (AD) is genetically linked to the processing of amyloid b protein precursor (AbPP). Aside from being the precursor of the Amyloid beta (Ab) found in plaques in the brains of patients with AD, little is known regarding the functional ro le of AbPP. We have recently reported biochemical evidence linking AbPP to the JNK signaling cascade by finding that JNK Interacting Protein-1 (JIP-1) binds AbPP.

In order to study the functional implications of this interaction we assayed the carboxyl t e rminal of AbPP for phosphorylation. We found that the threonine 668 within the AbPP 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 req uired for this process. We also found that JIP-1 only facilitated phosphorylation of AbPP but not of the two other family members APLP1 (Amyloid Precursor Like Protein 1) and APLP2. Understanding the connection between AbPP phosphorylation and the JNK signaling pathway which mediates the cells response to stress may have important implications in understanding the pathogenesis of Alzheimers Disease.

PMID: 12917434 [PubMed – as supplied by publisher]

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