Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45
Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45
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DOI：
10.1016/j.bcmd.2005.12.035
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发表时间：
2006-03-01
影响因子：
2.3
通讯作者：
Broxmeyer, HE
中科院分区：
文献类型：
--
作者：
Okabe, S;Tauchi, T;Broxmeyer, HE
基质细胞衍生因子-1 α（SDF 1 α/CXCL 12）是T细胞的有效化学引诱物。我们报道了Cbl家族成员Cbl和Cbl-b在SDF-1 α/CXCL 12刺激Jurkat T细胞后被酪氨酸磷酸化。增强的Cbl和Cbl-b的磷酸化受到src家族激酶的调节，可能还有Fyn。在SDF-1 α/CXCL 12刺激后，活化的Cbl和Cbl-b与Crk-L、Zap-70、Nck、PLC-γ和Fyb相互作用，暗示这些蛋白质与SDF-1 α/CXCL 12作用相关。SDF-1 α/CXCL 12在Lck缺陷型T细胞系J.CaM1.6或CD 45缺陷型T细胞系J45.01中不诱导Cbl或Cbl-b的酪氨酸磷酸化。因此，Lck Src激酶和酪氨酸磷酸酶CD 45可能参与调节Cbl家族成员的活化。Cbl和Cbl-b在迁移中的功能作用通过在T细胞系中SDF-1/CXCL 12诱导的迁移的减少来证明，其中转染Cbl和Cbl-b的小干扰RNA降低Cbl和Cbl-b的表达，但不降低MAPK活性。SDF-1 α/CXCL 12诱导的趋化性在CD 45缺陷型T细胞系中大大降低。我们的结果表明CD 45、Cbl-b、Src激酶和其他潜在相关蛋白质是SDF-1 alpha/CXCL 12诱导的Jurkat T细胞细胞迁移的介导剂。(c)2006年爱思唯尔公司All rights reserved.
Stromal-cell-derived factor-1 alpha (SDF1 alpha/CXCL12) is a potent chemoattractant for T cells. We report that Cbl family members, Cbl and Cbl-b, are tyrosine-phosphorylated after SDF-1 alpha/CXCL12 stimulation of Jurkat T cells. Enhanced phosphorylation of Cbl and Cbl-b was regulated by src family kinases, and perhaps Fyn. Activated Cbl and Cbl-b interacted with Crk-L, Zap-70, Nck, PLC-gamma and Fyb after SDF-1 alpha/CXCL12 stimulation, implicating association of these proteins in SDF-1 alpha/CXCL12 actions. SDF-1 alpha/CXCL12 did not induce tyrosine phosphorylation of Cbl or Cbl-b in Lck-deficient T cell line J.CaM1.6 or CD45-deficient T cell line J45.01. Thus, Lck Src kinase and tyrosine phosphatase CD45 are likely involved in regulating activation of Cbl family members. A functional role for Cbl and Cbl-b in migration was demonstrated by the decrease in SDF-1/CXCL12-induced migration in a T cell line in which transfected small interfering RNA for Cbl and Cbl-b decreased expression of Cbl and Cbl-b, but not MAPK activity. SDF-1 alpha/CXCL12-induced chemotaxis was greatly reduced in the CD45-deficient T cell line. Our results implicate CD45, Cbl, Cbl-b, src kinases and potentially other associated proteins as mediators of SDF-1 alpha/CXCL12-induced cell migration of Jurkat T cells. (c) 2006 Elsevier Inc. All rights reserved.