Auto-thiophosphorylation activity of Src tyrosine kinase

作者:Cabail M Zulema; Chen Emily I; Koller Antonius; Miller W Todd*
来源:BMC Biochemistry, 2016, 17(1): 13.
DOI:10.1186/s12858-016-0071-z

摘要

Background: Intermolecular autophosphorylation at Tyr416 is a conserved mechanism of activation among the members of the Src family of nonreceptor tyrosine kinases. Like several other tyrosine kinases, Src can catalyze the thiophosphorylation of peptide and protein substrates using ATP gamma S as a thiophosphodonor, although the efficiency of the reaction is low. Results: Here, we have characterized the ability of Src to auto-thiophosphorylate. Auto-thiophosphorylation of Src at Tyr416 in the activation loop proceeds efficiently in the presence of Ni2+, resulting in kinase activation. Other tyrosine kinases (Ack1, Hck, and IGF1 receptor) also auto-thiophosphorylate in the presence of Ni2+. Tyr416-thiophosphorylated Src is resistant to dephosphorylation by PTP1B phosphatase. Conclusions: Src and other tyrosine kinases catalyze auto-thiophosphorylation in the presence of Ni2+. Thiophosphorylation of Src occurs at Tyr416 in the activation loop, and results in enhanced kinase activity. Tyr416-thiophosphorylated Src could serve as a stable, persistently-activated mimic of Src.

  • 出版日期2016-7-7