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

CAS-L还参与了B和T细胞中的β1整合素或抗原受体介导的信号转导。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信号通路。免疫沉淀实验表明，全长Cas-L的单个结构域的缺失完全取消了其与Smad6和Smad7的对接功能，提示Cas-L的天然结构是其与Smad6和Smad7结合所必需的。最后，Cas-L被小干扰RNA寡核苷酸耗尽，减弱了转化生长因子-β对Huh-7细胞的生长抑制，伴随着Smad2和Smad3的磷酸化减少。这些结果强烈地表明，CaS-L是转化生长因子-β信号通路的潜在调节者。在变态反应性疾病中，嗜碱性粒细胞从血流迁移到炎症组织部位。由于跨基底膜迁移是局部嗜碱性粒细胞聚集的重要步骤，我们使用一个模型基底膜进行了人嗜碱细胞迁移实验。我们的结果表明，嗜碱性粒细胞对跨基底膜的迁移具有独特的调节机制，该机制受细胞因子、趋化物质、β2整合素和MMPs的影响，尤其是MMP9。基质金属蛋白酶-9可能在变态反应性疾病局部嗜碱性粒细胞大量涌入的发病机制中起重要作用。

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.