A Scaffold Protein JIP-1b Enhances Amyloid Precursor Protein Phosphorylation by JNK and Its Association with Kinesin Light Chain 1*
- Hidehiko Inomata‡,
- Yoshitaka Nakamura‡,
- Akira Hayakawa‡,
- Hiroyuki Takata‡,
- Toshiharu Suzuki§,
- Keiji Miyazawa‡ and
- Naomi Kitamura‡¶
- ‡Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan and the §Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
- ↵¶To whom correspondence should be addressed: Dept. of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan. Tel.: 81-45-924-5701; Fax: 81-45-924-5771; E-mail: nkitamur{at}bio.titech.ac.jp.
Abstract
Amyloid precursor protein (APP) is the precursor molecule of β-amyloid peptides, the major components of amyloid plaque in patients with Alzheimer's disease. In this study, we isolated JIP-1b, a JNK signaling scaffold protein, as a binding protein of APP, and analyzed the roles of JIP-1b in APP phosphorylation by JNK and the association of kinesin light chain 1 with APP. APP phosphorylation at threonine 668 by JNK was enhanced on the JIP-1b scaffold in vitro and in cultured cells exogenously expressing APP. APP phosphorylation in nerve growth factor-differentiated PC12 cells was mediated by activation of JNK signaling. JIP-1b also enhanced the association of kinesin light chain 1 with APP. Our results suggest that JIP-1b may function as a protein linking the kinesin-I motor protein to the cargo receptor, APP, and that the JNK signaling pathway may regulate the phosphorylation of this cargo protein through the JIP-1b scaffold.
- Received December 1, 2002.
- Revision received March 5, 2003.
- The American Society for Biochemistry and Molecular Biology, Inc.
