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

作者：Weir Marion E; Mann Jacqueline E; Corwin Thomas; Fulton Zachary W; Hao Jennifer M; Maniscalco Jeanine F; Kenney Marie C; Roman Roque Kristal M; Chapdelaine Elizabeth F; Stelzl Ulrich; Deming Paula B; Ballif Bryan A; Hinkle Karen L

来源：FEBS LETTERS, 2016, 590(8): 1042-1052.

DOI：10.1002/1873-3468.12144

• mass spectrometry
• phosphorylation
• Src family kinase

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.

• 出版日期2016-4