SRC-induced disassembly of adherens junctions requires localized phosphorylation and degradation of the rac activator tiam1.
Authors
Woodcock, Simon ARooney, Claire M
Liontos, Michalis
Connolly, Yvonne
Zoumpourlis, Vassilis
Whetton, Anthony D
Gorgoulis, Vassilis G
Malliri, Angeliki
Affiliation
Cell Signalling Group, Cancer Research UK Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.Issue Date
2009-03-13
Metadata
Show full item recordAbstract
The Rac activator Tiam1 is required for adherens junction (AJ) maintenance, and its depletion results in AJ disassembly. Conversely, the oncoprotein Src potently induces AJ disassembly and epithelial-mesenchymal transition (EMT). Here, we show that Tiam1 is phosphorylated on Y384 by Src. This occurs predominantly at AJs, is required for Src-induced AJ disassembly and cell migration, and creates a docking site on Tiam1 for Grb2. We find that Tiam1 is associated with ERK. Following recruitment of the Grb2-Sos1 complex, ERK becomes activated and triggers the localized degradation of Tiam1 at AJs, likely involving calpain proteases. Furthermore, we demonstrate that, in human tumors, Y384 phosphorylation positively correlates with Src activity, and total Tiam1 levels are inversely correlated. Thus, our data implicate Tiam1 phosphorylation and consequent degradation in Src-mediated EMT and resultant cell motility and establish a paradigm for regulating local concentrations of Rho-GEFs.Citation
SRC-induced disassembly of adherens junctions requires localized phosphorylation and degradation of the rac activator tiam1. 2009, 33 (5):639-53 Mol. CellJournal
Molecular CellDOI
10.1016/j.molcel.2009.02.012PubMed ID
19285946Type
ArticleLanguage
enISSN
1097-4164ae974a485f413a2113503eed53cd6c53
10.1016/j.molcel.2009.02.012
Scopus Count
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