Complex phosphorylation dynamics control the composition of the Syk interactome in B cells

被引:38
作者
Bohnenberger, Hanibal [1 ]
Oellerich, Thomas [1 ]
Engelke, Michael [1 ]
Hsiao, He-Hsuan [2 ]
Urlaub, Henning [2 ]
Wienands, Juergen [1 ]
机构
[1] Univ Gottingen, Inst Cellular & Mol Immunol, D-37073 Gottingen, Germany
[2] Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry Grp, D-37077 Gottingen, Germany
关键词
B-cell activation; Interactome; Spleen tyrosine kinase; 14-3-3; SPLEEN TYROSINE KINASE; ANTIGEN RECEPTOR; STRUCTURAL BASIS; SIGNALING PROTEINS; SH2; DOMAINS; ACTIVATION; TARGET; SLP-65; LOCALIZATION; INHIBITION;
D O I
10.1002/eji.201041326
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Spleen tyrosine kinase Syk provides critical transducer functions for a number of immune cell receptors and has been implicated in the generation of several forms of leukemias. Catalytic activity and the ability of Syk to interact with other signaling elements depend on the phosphorylation status of Syk. We have now identified and quantified the full spectrum of phosphoacceptor sites in human Syk as well as the interactome of Syk in resting and activated B cells by high-resolution mass spectrometry. While the majority of inducible phosphorylations occurred on tyrosine residues, one of the most frequently detected phosphosites encompassed serine 297 located within the linker insert distinguishing the long and short isoforms of Syk. Full-length Syk can associate with more than 25 distinct ligands including the 14-3-3 gamma adaptor protein, which binds directly to phosphoserine 297. The latter complex attenuates inducible plasma membrane recruitment of Syk, thereby limiting antigen receptor-proximal signaling pathways. Collectively, the established ligand library provides a basis to understand the complexity of the Syk signaling network.
引用
收藏
页码:1550 / 1562
页数:13
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