Tyrosine 416 Is Phosphorylated in the Closed, Repressed Conformation of c-Src

S Irtegun; RJ Wood; AR Ormsby; TD Mulhern; DM Hatters

Journal article

Tyrosine 416 Is Phosphorylated in the Closed, Repressed Conformation of c-Src

S Irtegun, RJ Wood, AR Ormsby, TD Mulhern, DM Hatters

Plos One | PUBLIC LIBRARY SCIENCE | Published : 2013

DOI: 10.1371/journal.pone.0071035

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Abstract

c-Src kinase activity is regulated by phosphorylation of Y527 and Y416. Y527 phosphorylation stabilizes a closed conformation, which suppresses kinase activity towards substrates, whereas phosphorylation at Y416 promotes an elevated kinase activity by stabilizing the activation loop in a manner permissive for substrate binding. Here we investigated the correlation of Y416 phosphorylation with c-Src activity when c-Src was locked into the open and closed conformations (by mutations Y527F and Q528E, P529E, G530I respectively). Consistent with prior findings, we found Y416 to be more greatly phosphorylated when c-Src was in an open, active conformation. However, we also observed an appreciable ..

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University of Melbourne Researchers

Terry Mulhern Author

Danny M Hatters Author

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Awarded by Australian Research Council

Funding Acknowledgements

This work was funded by grants to DMH (NHMRC project grants 566640, APP1049458, APP1049459; ARC Discovery grant DP120102763). DMH was a Grimwade Fellow, supported by the Miegunyah Trust and is currently an ARC Future Fellow (FT120100039). The University of Melbourne also provided support for DMH and TDM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.