Inomata H, Nakamura Y, Hayakawa A, Takata H, Suzuki T, Miyazawa K, Kitamura N. A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1. J Biol Chem. 2003 Jun 20;278(25):22946-55. PubMed.
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In a detailed and carefully performed study, Inomata and colleagues provide some intriguing new observations about what JIP-1b may be doing when it interacts with AβPP. Last year, several labs reported that AβPP interacts with JIP-1b, the JNK interacting scaffold protein (see Tare et al., 2002; Matsuda et al., 2002). It was never clear what this interaction meant. Now, the authors provide new data to indicate that this interaction facilitates JNK phosphorylation of AβPP, although, parenthetically, JNK does not require JIP-1b to phosphorylate AβPP. More interesting is the second observation in the study: The authors suggest that JIP-1b may be a required intermediate to bring AβPP together with kinesin light chain (KLC1). Goldstein and colleagues reported two years ago that AβPP directly interacts with kinesin light chain 1 (KLC1), and that AβPP may be the molecule that links certain axonal cargo vesicles to the kinesin machinery (see ARF related news story). This was a very attractive idea, as AβPP was known to undergo fast axonal transport. The problem is that other investigators have not replicated this finding. Therefore, Inomata and colleagues may have provided the critical piece of evidence showing that KLC1 and AβPP do come together, but only with JIP-1b as a scaffold. Finally, it has been shown that AβPP phosphorylation at Thr668 may be involved in neurite outgrowth. Thus, JIP-1b may play dual roles, not only bringing AβPP down the axon, but also facilitating its phosphorylation by JNK. Whether the latter is only in response to JNK signaling or related to what AβPP might normally do in axonal terminals is unclear.
References:
Taru H, Kirino Y, Suzuki T. Differential roles of JIP scaffold proteins in the modulation of amyloid precursor protein metabolism. J Biol Chem. 2002 Jul 26;277(30):27567-74. PubMed.
Matsuda S, Yasukawa T, Homma Y, Ito Y, Niikura T, Hiraki T, Hirai S, Ohno S, Kita Y, Kawasumi M, Kouyama K, Yamamoto T, Kyriakis JM, Nishimoto I. c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK. J Neurosci. 2001 Sep 1;21(17):6597-607. PubMed.
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