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

ABSTRACT: 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.

SUBMITTER: Weir ME

PROVIDER: S-EPMC4844773 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Weir Marion E ME Mann Jacqueline E JE Corwin Thomas T Fulton Zachary W ZW Hao Jennifer M JM Maniscalco Jeanine F JF Kenney Marie C MC Roman Roque Kristal M KM Chapdelaine Elizabeth F EF Stelzl Ulrich U Deming Paula B PB Ballif Bryan A BA Hinkle Karen L KL

FEBS letters 20160413 8

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 dom ...[more]

PMID: 27001024

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