Cutting edge: Bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with slits and act as negative regulators of monocyte chemotaxis
Cutting edge: Bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with slits and act as negative regulators of monocyte chemotaxis
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DOI：
10.4049/jimmunol.173.10.5914
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发表时间：
2004-11-15
影响因子：
4.4
通讯作者：
Yang, D
中科院分区：
文献类型：
--
作者：
Chen, B;Blair, DG;Yang, D
DRM/Gremlin和DAN是两种同源的分泌型骨形态发生蛋白拮抗剂，已被证明调节早期发育、肿瘤发生和肾脏病理生理。在本研究中，我们报道了DRM和DAN与Slit1和Slit2蛋白在物理和功能上的相互作用。DRM与SLITS的结合依赖于其糖基化，不受骨形态发生蛋白的干扰。重要的是，DRM和DAN对基质细胞衍生因子1α(SDF-1α)或fMLP诱导的单核细胞迁移具有抑制作用。丹参酮抑制SDF-1α诱导的单核细胞趋化作用不是由于阻断了SDF-1α与其受体的结合。因此，结果证实DRM和DAN可以与Sit蛋白相互作用，并作为单核细胞趋化的抑制剂，显示了这些蛋白以前未知的生物学作用。
Drm/Gremlin and Dan, two homologous secreted antagonist of bone morphogenic proteins have been shown to regulate early development, tumorigenesis, and renal pathophysiology. In this study, we report that Drm and Dan physically and functionally interact with Slit1 and Slit2 proteins. Drm binding to Slits depends on its glycosylation and is not interfered with by bone morphogenic proteins. Importantly, Drm and Dan function as inhibitors for monocyte migration induced by stromal cell-derived factor 1alpha (SDF-1alpha) or fMLP. The inhibition of SDF-1alpha-induced monocyte chemotaxis by Dan is not due to blocking the binding of SDF-1alpha to its receptor. Thus, the results identify that Drm and Dan can interact with Slit proteins and act as inhibitors of monocyte chemotaxis, demonstrating a previously unidentified biological role for these proteins.