Novel autophosphorylation sites of Src family kinases regulate kinase activity and SH2 domain-binding capacity.

Autor: Weir ME; Department of Biology, University of Vermont, Burlington, VT, USA., Mann JE; Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, VT, USA., Corwin T; Otto-Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany., Fulton ZW; Department of Biology, University of Vermont, Burlington, VT, USA.; Department of Biology and Physical Education, Norwich University, Northfield, VT, USA., Hao JM; Department of Biology, University of Vermont, Burlington, VT, USA., Maniscalco JF; Department of Biology, University of Vermont, Burlington, VT, USA., Kenney MC; Department of Biology, University of Vermont, Burlington, VT, USA., Roman Roque KM; Department of Biology, University of Vermont, Burlington, VT, USA., Chapdelaine EF; Department of Biology, University of Vermont, Burlington, VT, USA.; Department of Biology and Physical Education, Norwich University, Northfield, VT, USA., Stelzl U; Otto-Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany., Deming PB; Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, VT, USA., Ballif BA; Department of Biology, University of Vermont, Burlington, VT, USA., Hinkle KL; Department of Biology, University of Vermont, Burlington, VT, USA.; Department of Biology and Physical Education, Norwich University, Northfield, VT, USA.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2016 Apr; Vol. 590 (8), pp. 1042-52. Date of Electronic Publication: 2016 Apr 13.
DOI: 10.1002/1873-3468.12144
Abstrakt: Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the C-terminal site to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain.
(© 2016 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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