A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1.
Amyloid precursor protein (APP) is the precursor molecule of beta-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.
Inomata
Hidehiko
H
Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Nakamura
Yoshitaka
Y
Hayakawa
Akira
A
Takata
Hiroyuki
H
Suzuki
Toshiharu
T
Miyazawa
Keiji
K
Kitamura
Naomi
N
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D016547:Kinesins; D020935:MAP Kinase Signaling System / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; C000715690:Klc1 protein, rat; C490666:MAPK8IP1 protein, human; C110528:Mapk8ip1 protein, rat; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016547:Kinesins