TY - JOUR
T1 - Interaction of ASK1 and the β-amyloid precursor protein in a stress-signaling complex
AU - Galvan, Veronica
AU - Banwait, Surita
AU - Spilman, Patricia
AU - Gorostiza, Olivia F.
AU - Peel, Alyson
AU - Ataie, Marina
AU - Crippen, Danielle
AU - Huang, Wei
AU - Sidhu, Gurleen
AU - Ichijo, Hidenori
AU - Bredesen, Dale E.
N1 - Funding Information:
We thank Drs. Alexei Kurakin, Christopher Link, and Anders Olsen for helpful discussions and insights; Dr. Lennart Mucke for the PDAPP transgenic mice and Dr. Edward Koo for valuable reagents. We also thank Molly Susag for revising and editing the manuscript and Marina Ataie and Diba Ataie for excellent technical assistance. This work was supported in part by National Institutes of Health Grants (AG05131, AG12282, NS33376 and NS45093) and the Joseph Drown Foundation to DB, and the Alzheimer’s Association NIRG-04-1054 and John D. French Alzheimer’s Foundation to VG. VG specially thanks Mrs. Eloise Goodhew Barnett for her support.
PY - 2007/10
Y1 - 2007/10
N2 - The amyloid precursor protein (APP) is a type I transmembrane protein translocated to neuronal terminals, whose function is still unknown. The C-terminus of APP mediates its interaction with cellular adaptor and signaling proteins, some of which signal to the stress-activated protein kinase (SAPK) pathway. Here we show that ASK1, a MAPKKK that activates two SAPKs, c-Jun N-terminal-kinase (JNK) and p38, is present in a complex containing APP, phospho-MKK6, JIP1 and JNK1. In primary neurons deprived of growth factors, as well as in brains of (FAD)APP-transgenic mice, ASK1 was upregulated in neuronal projections, where it interacted with APP. In non-transgenic brains, ASK1 and APP associated mainly in the ER. Our results indicate that recruitment of ASK1 to stress-signaling complexes assembled with APP may be triggered and enhanced by cellular stress. Thus, ASK1 may be the apical MAPKKK in a signaling complex assembled with APP as a response to stress.
AB - The amyloid precursor protein (APP) is a type I transmembrane protein translocated to neuronal terminals, whose function is still unknown. The C-terminus of APP mediates its interaction with cellular adaptor and signaling proteins, some of which signal to the stress-activated protein kinase (SAPK) pathway. Here we show that ASK1, a MAPKKK that activates two SAPKs, c-Jun N-terminal-kinase (JNK) and p38, is present in a complex containing APP, phospho-MKK6, JIP1 and JNK1. In primary neurons deprived of growth factors, as well as in brains of (FAD)APP-transgenic mice, ASK1 was upregulated in neuronal projections, where it interacted with APP. In non-transgenic brains, ASK1 and APP associated mainly in the ER. Our results indicate that recruitment of ASK1 to stress-signaling complexes assembled with APP may be triggered and enhanced by cellular stress. Thus, ASK1 may be the apical MAPKKK in a signaling complex assembled with APP as a response to stress.
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Apoptosis signaling kinase
KW - Neurodegeneration
KW - Stress signaling complex
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U2 - 10.1016/j.nbd.2007.06.017
DO - 10.1016/j.nbd.2007.06.017
M3 - Article
C2 - 17719230
AN - SCOPUS:34548773391
VL - 28
SP - 65
EP - 75
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 1
ER -