Journal article
Tau interacts with SHP2 in neuronal systems and in Alzheimer's disease brains
Journal of cell science, Vol.132(14), p.jcs229054
07/15/2019
DOI: 10.1242/jcs.229054
PMCID: PMC6679582
PMID: 31201283
Abstract
Microtubule-associated protein tau, an integral component of neurofibrillary tangles, interacts with a variety of signaling molecules. Previously, our laboratory reported that nerve growth factor (NGF)-induced MAPK activation in a PC12-derived cell line was potentiated by tau, with phosphorylation at T231 being required. Therefore, we sought to identify a signaling molecule involved in the NGF-induced Ras-MAPK pathway that interacted with phospho-T231-tau. Here, we report that the protein tyrosine phosphatase SHP2 (also known as PTPN11) interacted with tau, with phospho-T231 significantly enhancing the interaction. By using proximity ligation assays, we found that endogenous tau–SHP2 complexes were present in neuronal cells, where the number of tau–SHP2 complexes significantly increased when the cells were treated with NGF, with phosphorylation at T231 being required for the increase. The interaction did not require microtubule association, and an association between tau and activated SHP2 was also found. Tau–SHP2 complexes were also found in both primary mouse hippocampal cultures and adult mouse brain. Finally, SHP2 levels were upregulated in samples from patients with mild and severe Alzheimer's disease (AD), and the level of tau–SHP2 complexes were increased in AD patient samples. These findings strongly suggest a role for the tau–SHP2 interaction in NGF-stimulated neuronal development and in AD.
This article has an associated First Person interview with the first author of the paper.
Highlighted Article:
Tau associates with SHP2, a protein tyrosine phosphatase that is involved in cancer. Tau–SHP2 complexes, regulated by tau phosphorylation, appear during neuronal development and in Alzheimer's disease samples.
Details
- Title: Subtitle
- Tau interacts with SHP2 in neuronal systems and in Alzheimer's disease brains
- Creators
- Yohan Kim - University of Iowa Carver College of MedicineGuanghao Liu - University of Iowa Carver College of MedicineChad J Leugers - University of Iowa Carver College of MedicineJoseph D Mueller - University of Iowa Carver College of MedicineMeghan B Francis - University of Iowa Carver College of MedicineMarco M Hefti - University of Iowa Carver College of MedicineJulie A Schneider - Rush Medical CollegeGloria Lee - University of Iowa Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.132(14), p.jcs229054
- DOI
- 10.1242/jcs.229054
- PMID
- 31201283
- PMCID
- PMC6679582
- NLM abbreviation
- J Cell Sci
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Publisher
- The Company of Biologists Ltd
- Grant note
- ; R01 AG017753; F30 AG054134 / ; IIRG-12-241042 / ;
- Language
- English
- Date published
- 07/15/2019
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984070767602771
Metrics
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