Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11990
Title: Activation of Src family tyrosine kinases by ferric ions.
Authors: Baldwin, Graham S;Lio, Daisy Sio-Seng;Ferrand, Audrey;Catimel, Bruno;Shehan, B Philip;Norton, Raymond S;Cheng, Heung-Chin
Affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Electronic address: grahamsb@unimelb.edu.au.
The University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia
Ludwig Institute for Cancer Research, Melbourne Branch, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 12-Dec-2013
Citation: Biochimica Et Biophysica Acta 2013; 1844(3): 487-96
Abstract: The Src-family tyrosine kinases (SFKs) are oncogenic enzymes that contribute to the initiation and progression of many types of cancer. In normal cells, SFKs are kept in an inactive state mainly by phosphorylation of a consensus regulatory tyrosine near the C-terminus (Tyr(530) in the SFK c-Src). As recent data indicate that tyrosine modification enhances binding of metal ions, the hypothesis that SFKs might be regulated by metal ions was investigated. The c-Src C-terminal peptide bound two Fe(3+) ions with affinities at pH4.0 of 33 and 252μM, and phosphorylation increased the affinities at least 10-fold to 1.4 and 23μM, as measured by absorbance spectroscopy. The corresponding phosphorylated peptide from the SFK Lyn bound two Fe(3+) ions with much higher affinities (1.2pM and 160nM) than the Src C-terminal peptide. Furthermore, when Lyn or Hck kinases, which had been stabilised in the inactive state by phosphorylation of the C-terminal regulatory tyrosine, were incubated with Fe(3+) ions, a significant enhancement of kinase activity was observed. In contrast Lyn or Hck kinases in the unphosphorylated active state were significantly inhibited by Fe(3+) ions. These results suggest that Fe(3+) ions can regulate SFK activity by binding to the phosphorylated C-terminal regulatory tyrosine.
Internal ID Number: 24334106
URI: http://ahro.austin.org.au/austinjspui/handle/1/11990
DOI: 10.1016/j.bbapap.2013.12.004
URL: http://www.ncbi.nlm.nih.gov/pubmed/24334106
Type: Journal Article
Subjects: Calcium
Ferric
Iron
Kinase
Phosphotyrosine
Amino Acid Sequence
Cations
Enzyme Activation
Ferric Compounds.metabolism
Molecular Sequence Data
Phosphorylation
Protein Binding
Surface Plasmon Resonance
src-Family Kinases.chemistry.metabolism
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.