RT Journal Article
SR Electronic
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.
FD Society for Neuroscience
SP 6597
OP 6607
DO 10.1523/JNEUROSCI.21-17-06597.2001
VO 21
IS 17
A1 Shuji Matsuda
A1 Takashi Yasukawa
A1 Yasuko Homma
A1 Yuko Ito
A1 Takako Niikura
A1 Takako Hiraki
A1 Shuichi Hirai
A1 Shigeo Ohno
A1 Yoshiko Kita
A1 Masaoki Kawasumi
A1 Keisuke Kouyama
A1 Tokuo Yamamoto
A1 John M. Kyriakis
A1 Ikuo Nishimoto
YR 2001
UL http://www.jneurosci.org/content/21/17/6597.abstract
AB 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.