Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase C gamma 1, Grb2, and Src family kinases

Reynolds, C. Hugh, Garwood, Claire J., Wray, Selina, Price, Caroline, Kellie, Stuart, Perera, Timothy, Zvelebil, Marketa, Yang, Alice, Sheppard, Paul W., Varndell, Ian M., Hanger, Diane P. and Anderton, Brian H. (2008) Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase C gamma 1, Grb2, and Src family kinases. The Journal of Biological Chemistry, 283 26: 18177-18186. doi:10.1074/jbc.M709715200

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ172777_OA.pdf Full text (open access) application/pdf 374.77KB 0

Author Reynolds, C. Hugh
Garwood, Claire J.
Wray, Selina
Price, Caroline
Kellie, Stuart
Perera, Timothy
Zvelebil, Marketa
Yang, Alice
Sheppard, Paul W.
Varndell, Ian M.
Hanger, Diane P.
Anderton, Brian H.
Title Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase C gamma 1, Grb2, and Src family kinases
Formatted title
Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cγ1, Grb2, and Src family kinases
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2008-06-27
Year available 2008
Sub-type Article (original research)
DOI 10.1074/jbc.M709715200
Open Access Status File (Publisher version)
Volume 283
Issue 26
Start page 18177
End page 18186
Total pages 10
Place of publication Bethesda, MD, USA
Publisher American Society for Biochemistry and Molecular Biology, Inc.
Language eng
Subject C1
060406 Genetic Immunology
970106 Expanding Knowledge in the Biological Sciences
Abstract The microtubule-associated protein tau can associate with various other proteins in addition to tubulin, including the SH3 domains of Src family tyrosine kinases. Tau is well known to aggregate to form hyperphosphorylated filamentous deposits in several neurodegenerative diseases (tauopathies) including Alzheimer disease. We now report that tau can bind to SH3 domains derived from the p85α subunit of phosphatidylinositol 3-kinase, phospholipase Cγ1, and the N-terminal (but not the C-terminal) SH3 of Grb2 as well as to the kinases Fyn, cSrc, and Fgr. However, the short inserts found in neuron-specific isoforms of Src prevented the binding of tau. The experimentally determined binding of tau peptides is well accounted for when modeled into the peptide binding cleft in the SH3 domain of Fyn. After phosphorylation in vitro or in transfected cells, tau showed reduced binding to SH3 domains; no binding was detected with hyperphosphorylated tau isolated from Alzheimer brain, but SH3 binding was restored by phosphatase treatment. Tau mutants with serines and threonines replaced by glutamate, to mimic phosphorylation, showed reduced SH3 binding. These results strongly suggest that tau has a potential role in cell signaling in addition to its accepted role in cytoskeletal assembly, with regulation by phosphorylation that may be disrupted in the tauopathies including Alzheimer disease.
Keyword Biochemistry & Molecular Biology
Biochemistry & Molecular Biology
BIOCHEMISTRY & MOLECULAR BIOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID G0300408
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 117 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 139 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 31 Mar 2009, 19:36:48 EST by Glenda Chown on behalf of School of Chemistry & Molecular Biosciences