TY - JOUR T1 - c-Jun N-Terminal Kinase (JNK)-Interacting Protein-1b/Islet-Brain-1 Scaffolds Alzheimer's Amyloid Precursor Protein with JNK JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6597 LP - 6607 DO - 10.1523/JNEUROSCI.21-17-06597.2001 VL - 21 IS - 17 AU - Shuji Matsuda AU - Takashi Yasukawa AU - Yasuko Homma AU - Yuko Ito AU - Takako Niikura AU - Takako Hiraki AU - Shuichi Hirai AU - Shigeo Ohno AU - Yoshiko Kita AU - Masaoki Kawasumi AU - Keisuke Kouyama AU - Tokuo Yamamoto AU - John M. Kyriakis AU - Ikuo Nishimoto Y1 - 2001/09/01 UR - http://www.jneurosci.org/content/21/17/6597.abstract N2 - Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)-interacting molecules by screening mouse and human brain libraries. In addition to known interacting proteins containing a phosphotyrosine-interaction-domain (PID)—Fe65, Fe65L, Fe65L2, X11, and mDab1, we identified, as a novel APP-interacting molecule, a PID-containing isoform of mouse JNK-interacting protein-1 (JIP-1b) and its human homolog IB1, the established scaffold proteins for JNK. The APP amino acids Tyr682, Asn684, and Tyr687 in the G681YENPTY687 region were all essential for APP/JIP-1b interaction, but neither Tyr653 nor Thr668 was necessary. APP-interacting ability was specific for this additional isoform containing PID and was shared by both human and mouse homologs. JIP-1b expressed by mammalian cells was efficiently precipitated by the cytoplasmic domain of APP in the extreme Gly681–Asn695 domain-dependent manner. Reciprocally, both full-length wild-type and familial Alzheimer's disease mutant APPs were precipitated by PID-containing JIP constructs. Antibodies raised against the N and C termini of JIP-1b coprecipitated JIP-1b and wild-type or mutant APP in non-neuronal and neuronal cells. Moreover, human JNK1β1 formed a complex with APP in a JIP-1b-dependent manner. Confocal microscopic examination demonstrated that APP and JIP-1b share similar subcellular localization in transfected cells. These data indicate that JIP-1b/IB1 scaffolds APP with JNK, providing a novel insight into the role of the JNK scaffold protein as an interface of APP with intracellular functional molecules. ER -