GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood.
GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood.
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DOI：
10.1126/science.1208248
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发表时间：
2011-09-30
期刊：
影响因子：
--
通讯作者：
Cyster JG
中科院分区：
文献类型：
--
作者：
Arnon TI;Xu Y;Lo C;Pham T;An J;Coughlin S;Dorn GW;Cyster JG
Lymphocytes egress from lymphoid organs in response to sphingosine-1-phosphate (S1P); minutes later they migrate from blood into tissue against the S1P gradient. The mechanisms facilitating cell movement against the gradient have not been defined. Here we show that G-protein coupled receptor kinase-2 (GRK2) functions in down-regulation of S1P receptor-1 (S1PR1) on blood-exposed lymphocytes. T- and B-cell movement from blood into lymph nodes is reduced in the absence of GRK2 but is restored in S1P-deficient mice. In the spleen, B-cell movement between the blood-rich marginal zone and follicles is disrupted by GRK2-deficiency and by mutation of an S1PR1 desensitization motif. Moreover, delivery of systemic antigen into follicles is impaired. Thus, GRK2-dependent S1PR1 desensitization allows lymphocytes to escape circulatory fluids and migrate into lymphoid tissues.
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DOI：
10.1016/s0074-7696(06)50005-1
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：
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DOI：
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发表时间：
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期刊：
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影响因子：
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