CLEC-2 activates Syk through dimerization.
CLEC-2 activates Syk through dimerization.
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DOI：
10.1182/blood-2009-08-237834
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发表时间：
2010-04-08
期刊：
影响因子：
20.3
通讯作者：
Watson SP
中科院分区：
文献类型：
--
作者：
Hughes CE;Pollitt AY;Mori J;Eble JA;Tomlinson MG;Hartwig JH;O'Callaghan CA;Fütterer K;Watson SP
C型凝集素受体CLEC-2通过Src和Syk酪氨酸激酶激活血小板，导致下游衔接蛋白和效应酶（包括PLCγ2）的酪氨酸磷酸化。信号传导通过位于CLEC-2胞质尾部中的YxxL序列中的单个保守酪氨酸的磷酸化启动。CLEC-2使用的信号传导途径与受体使用的信号传导途径有许多相似之处，所述受体在其胞质尾部或相关受体链中具有一个或多个由序列YxxL/Ix 6 - 12 YxxL/I定义的基于免疫受体酪氨酸的活化基序（ITAM）拷贝。保守ITAM酪氨酸的磷酸化通过结合Syk串联SH 2结构域促进Syk结合和活化。在这份报告中，我们提出的证据，使用肽下拉研究，表面等离子体共振，定量蛋白质印迹，色氨酸荧光测量和竞争实验，Syk激活CLEC-2介导的交联通过串联SH 2结构域的化学计量比为2：1。为了支持这一模型，交联和电子显微镜证实CLEC-2在静息血小板中作为二聚体存在，并在活化后转化为更大的复合物。这是通过单个含YxxL的受体激活Syk的独特模式。
The C-type lectin receptor CLEC-2 activates platelets through Src and Syk tyrosine kinases leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including PLCγ2. Signalling is initiated through phosphorylation of a single conserved tyrosine located in a YxxL sequence in the CLEC-2 cytosolic tail. The signalling pathway used by CLEC-2 shares many similarities with that used by receptors which have one or more copies of an immunoreceptor tyrosine-based activation motif (ITAM), defined by the sequence YxxL/Ix6–12YxxL/I, in their cytosolic tails or associated receptor chains. Phosphorylation of the conserved ITAM tyrosines promotes Syk binding and activation through binding of the Syk tandem SH2 domains. In this report we present evidence using peptide pull down studies, surface plasmon resonance, quantitative western blotting, tryptophan fluorescence measurements and competition experiments that Syk activation by CLEC-2 is mediated by the cross-linking through the tandem SH2 domains with a stoichiometry of 2:1. In support of this model, cross-linking and electron microscopy demonstrate that CLEC-2 is present as a dimer in resting platelets and converted to larger complexes upon activation. This is a unique mode of activation of Syk by a single YxxL-containing receptor.
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DOI：
10.1042/bj20071216
发表时间：
2008-04-01
期刊：
The Biochemical journal
影响因子：
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作者：
Christou CM;Pearce AC;Watson AA;Mistry AR;Pollitt AY;Fenton-May AE;Johnson LA;Jackson DG;Watson SP;O'Callaghan CA
通讯作者：
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DOI：
10.1084/jem.184.5.1663
发表时间：
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期刊：
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影响因子：
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作者：
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DOI：
10.4049/jimmunol.0802808
发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kerrigan AM;Dennehy KM;Mourão-Sá D;Faro-Trindade I;Willment JA;Taylor PR;Eble JA;Reis e Sousa C;Brown GD
通讯作者：
Brown GD
影响因子：
64.5
作者：
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影响因子：
4.8
作者：
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