Activation of Src family tyrosine kinases by ferric ions
| Autor: | Bruno Catimel, Audrey Ferrand, Graham S. Baldwin, Heung-Chin Cheng, B. Philip Shehan, Raymond S. Norton, Daisy Sio Seng Lio |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Tyrosine-protein kinase CSK
biology Chemistry Molecular Sequence Data Biophysics Surface Plasmon Resonance SRC Family Tyrosine Kinase Ferric Compounds Biochemistry Receptor tyrosine kinase Analytical Chemistry Enzyme Activation src-Family Kinases LYN Cations biology.protein Phosphorylation Amino Acid Sequence Tyrosine Molecular Biology Tyrosine kinase Protein Binding Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1844:487-496 |
| ISSN: | 1570-9639 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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