Complex phosphorylation dynamics control the composition of the Syk interactome in B cells
Complex phosphorylation dynamics control the composition of the Syk interactome in B cells
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DOI：
10.1002/eji.201041326
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Wienands, Juergen
中科院分区：
文献类型：
--
作者：
Bohnenberger, Hanibal;Oellerich, Thomas;Wienands, Juergen
脾酪氨酸激酶Syk为许多免疫细胞受体提供关键的转导功能，并与几种形式的白血病的产生有关。Syk的催化活性和与其他信号传导元件相互作用的能力取决于Syk的磷酸化状态。我们现在已经通过高分辨率质谱法鉴定和定量了人Syk中磷酸化受体位点的全谱以及Syk在静息和活化B细胞中的相互作用组。虽然大多数诱导型磷酸化发生在酪氨酸残基上，但最常检测到的磷酸化位点之一包括位于区分Syk的长和短同种型的接头插入物内的丝氨酸297。全长Syk可以与超过25种不同的配体结合，包括直接与磷酸丝氨酸297结合的14-3-3 γ衔接蛋白。后一种复合物减弱Syk的可诱导质膜募集，从而限制抗原受体近端信号传导途径。总的来说，已建立的配体库为理解Syk信号网络的复杂性提供了基础。
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.