Spatial coupling of JNK activation to the B cell antigen receptor by tyrosine-phosphorylated ezrin.
Spatial coupling of JNK activation to the B cell antigen receptor by tyrosine-phosphorylated ezrin.
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DOI：
10.4049/jimmunol.1201292
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Gupta N
中科院分区：
文献类型：
--
作者：
Parameswaran N;Enyindah-Asonye G;Bagheri N;Shah NB;Gupta N
The Ezrin-Radixin-Moesin (ERM) proteins regulate B lymphocyte activation via their effect on BCR diffusion and microclustering. This relies on their ability to dynamically tether the plasma membrane with actin filaments that is in turn facilitated by phosphorylation of the conserved threonine residue in the actin-binding domain. Here, we describe a novel function of ezrin in regulating JNK activation that is mediated by phosphorylation of a tyrosine (Y353) residue that is unconserved with moesin and radixin. BCR, but not CD40, TLR4 or CXCR5 stimulation, induced phosphorylation of ezrin at Y353 in mouse splenic B cells. Ezrin existed in a preformed complex with Syk in unstimulated B cells and underwent Syk-dependent phosphorylation upon anti-IgM stimulation. Y353-phosphorylated ezrin co-localized with the BCR within minutes of stimulation and co-trafficked with the endocytosed BCRs through the early and late endosomes. The T567 residue of ezrin was rephosphorylated in late endosomes and at the plasma membrane at later times of BCR stimulation. Expression of a non-phosphorylatable Y353F mutant of ezrin specifically impaired JNK activation. BCR crosslinking induced the association of Y353-phosphorylated ezrin with JNK and its kinase MKK7, and spatial co-localization with phosphorylated JNK in the endosomes. The YFP-tagged Y353F mutant displayed reduced co-localization with the endocytosed BCR as compared to wild type Ezrin-YFP. Taken together, our data identify a novel role for ezrin as a spatial adaptor that couples JNK signaling components to the BCR signalosome, thus facilitating JNK activation.
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DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
影响因子：
8.5
作者：
Engstrom, W.;Ward, A.;Moorwood, K.
通讯作者：
Moorwood, K.
DOI：
10.1083/jcb.200707199
发表时间：
2007-11-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ilani T;Khanna C;Zhou M;Veenstra TD;Bretscher A
通讯作者：
Bretscher A
影响因子：
30.5
作者：
Chaturvedi, Akanksha;Martz, Rebecca;Pierce, Susan K.
通讯作者：
Pierce, Susan K.
影响因子：
64.5
作者：
Pearson, MA;Reczek, D;Karplus, PA
通讯作者：
Karplus, PA