Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA.
J Biol Chem. 2010 Dec 17;285(51):39844-54. doi: 10.1074/jbc.M110.164509. Epub 2010 Oct 18.
The Syk protein-tyrosine kinase is phosphorylated on multiple tyrosines after the aggregation of the B cell antigen receptor. However, metabolic labeling experiments indicate that Syk is inducibly phosphorylated to an even greater extent on serine after receptor ligation. A combination of phosphopeptide mapping and mass spectrometric analyses indicates that serine 291 is a major site of phosphorylation. Serine 291 lies within a 23-amino acid insert located within the linker B region that distinguishes Syk from SykB and Zap-70. The phosphorylation of serine-291 by protein kinase C enhances the ability of Syk to couple the antigen receptor to the activation of the transcription factors NFAT and Elk-1. Protein interaction studies indicate a role for the phosphorylated linker insert in promoting an interaction between Syk and the chaperone protein, prohibitin.
Syk 蛋白酪氨酸激酶在 B 细胞抗原受体聚集后，其多个酪氨酸残基被磷酸化。然而，代谢标记实验表明，在受体交联后，Syk 丝氨酸的可诱导磷酸化程度甚至更大。磷酸肽图谱和质谱分析的组合表明丝氨酸 291 是磷酸化的主要位点。丝氨酸 291 位于区分 Syk 与 SykB 和 Zap-70 的连接 B 区的 23 个氨基酸插入物内。蛋白激酶 C 对丝氨酸 291 的磷酸化增强了 Syk 将抗原受体与转录因子 NFAT 和 Elk-1 的激活偶联的能力。蛋白相互作用研究表明，磷酸化的连接插入物在促进 Syk 与伴侣蛋白 prohibitin 之间的相互作用中起作用。
