Cortactin is a functional target of E-cadherin-activated Src family kinases in MCF7 epithelial monolayers

Ren, Gang, Helwani, Falak M., Verma, Suzie, McLachlan, Robert W., Weed, Scott A. and Yap, Alpha S. (2009) Cortactin is a functional target of E-cadherin-activated Src family kinases in MCF7 epithelial monolayers. Journal of Biological Chemistry, 284 28: 18913-18922. doi:10.1074/jbc.M109.000307

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Author Ren, Gang
Helwani, Falak M.
Verma, Suzie
McLachlan, Robert W.
Weed, Scott A.
Yap, Alpha S.
Title Cortactin is a functional target of E-cadherin-activated Src family kinases in MCF7 epithelial monolayers
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2009-07-10
Year available 2009
Sub-type Article (original research)
DOI 10.1074/jbc.M109.000307
Open Access Status File (Publisher version)
Volume 284
Issue 28
Start page 18913
End page 18922
Total pages 10
Editor Herbert Tabor
Place of publication Bethesda, MD, U. S. A.
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
0304 Medicinal and Biomolecular Chemistry
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Abstract Src family kinases (SFKs) signal in response to E-cadherin to support cadherin adhesion and the integrity of cell-cell contacts (McLachlan, R. W., Kraemer, A., Helwani, F. M., Kovacs, E. M., and Yap, A. S. ( 2007) Mol. Biol. Cell 18, 3214-3223). We now identify the actin-regulatory protein, cortactin, as a target of E-cadherin-activated SFK signaling. Tyr-phosphorylated cortactin was found at cell-cell contacts in established epithelial monolayers, and cortactin became acutely tyrosine-phosphorylated when E-cadherin adhesion was engaged. In all circumstances, cortactin tyrosine phosphorylation was blocked by inhibiting SFK signaling. Importantly, Tyr-phosphorylated cortactin was necessary to preserve the integrity of cadherin contacts and the perijunctional actin cytoskeleton. Moreover, expression of a phosphomimetic cortactin mutant could prevent SFK blockade from disrupting cadherin organization, thereby placing cortactin functionally downstream of SFK signaling at cadherin adhesions. We conclude that SFK and cortactin constitute an important signaling pathway that functionally links E-cadherin adhesion and the actin cytoskeleton.
Formatted abstract
Src family kinases (SFKs) signal in response to E-cadherin to support cadherin adhesion and the integrity of cell-cell contacts (McLachlan, R. W., Kraemer, A., Helwani, F. M., Kovacs, E. M., and Yap, A. S. (2007) Mol. Biol. Cell 18, 3214–3223). We now identify the actin-regulatory protein, cortactin, as a target of E-cadherin-activated SFK signaling. Tyr-phosphorylated cortactin was found at cell-cell contacts in established epithelial monolayers, and cortactin became acutely tyrosine-phosphorylated when E-cadherin adhesion was engaged. In all circumstances, cortactin tyrosine phosphorylation was blocked by inhibiting SFK signaling. Importantly, Tyr-phosphorylated cortactin was necessary to preserve the integrity of cadherin contacts and the perijunctional actin cytoskeleton. Moreover, expression of a phosphomimetic cortactin mutant could prevent SFK blockade from disrupting cadherin organization, thereby placing cortactin functionally downstream of SFK signaling at cadherin adhesions. We conclude that SFK and cortactin constitute an important signaling pathway that functionally links E-cadherin adhesion and the actin cytoskeleton.
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Keyword Cell-cell-adhesion
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under "Molecular Basis of Cell and Developmental Biology"

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 17:53:30 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience