The role of Integrin-downstream signaling molecules in the expression of chemokine receptors

Cas-L还参与B细胞和T细胞中β 1整合素或抗原受体介导的信号传导。在本研究中，我们证明了Cas-L通过与Smad6和Smad7相互作用来增强转化生长因子- β (tgf - β)信号通路。免疫沉淀实验显示，全长Cas-L的单域缺失完全取消了其与Smad6和Smad7的对接功能，这表明Cas-L的天然结构是其与Smad6和Smad7的关联所必需的。最后，通过小干扰RNA寡核苷酸耗尽Cas-L可减弱tgf - β诱导的Huh-7细胞的生长抑制，同时降低Smad2和Smad3的磷酸化。这些结果强烈提示Cas-L是tgf - β信号通路的潜在调节因子。在过敏性疾病中，嗜碱性粒细胞从血流迁移到发炎的组织部位。由于跨基底膜迁移是局部嗜碱性粒细胞积累的重要步骤，我们使用模型基底膜进行了人类嗜碱性粒细胞迁移试验。我们的研究结果表明，嗜碱性细胞具有独特的跨基底膜迁移调控机制，该机制受细胞因子、趋化剂、β 2整合素和MMPs，特别是MMP-9的影响。MMP-9可能在过敏性疾病中局部嗜碱性粒细胞内流的发病机制中起关键作用。

Cas-L is also involved in beta1 integrin- or antigen receptor-mediated signaling in B and T cells. In the present study, we demonstrate that Cas-L potentiates transforming growth factor-beta (TGF-beta) signaling pathway by interacting with Smad6 and Smad7. Immunoprecipitation experiments reveal that single domain deletion of full-length Cas-L completely abolishes its docking function with Smad6 and Smad7, suggesting that the natural structure of Cas-L is necessary for its association with Smad6 and Smad7. Finally, depletion of Cas-L by small-interfering RNA oligo attenuates TGF-beta-induced growth inhibition of Huh-7 cells, with a concomitant reduction in phosphorylation of Smad2 and Smad3. These results strongly suggest that Cas-L is a potential regulator of TGF-beta signaling pathway.In allergic disorders, basophils migrate from the blood stream to inflamed tissue sites. Since trans-basement membrane migration is an important step for local basophil accumulation, we performed a human basophil transmigration assay using a model basement membrane. Our results suggest that basophils possess a unique regulatory mechanism for trans-basement membrane migration which is affected by cytokines, chemoattractants, beta2 integrin and MMPs, especially MMP-9. MMP-9 may be critically involved in the pathogenesis of local basophil influx in allergic diseases.