Chen Bo, Blair Donald G, Plisov Sergei, Vasiliev Gennady, Perantoni Alan O, Chen Qian, Athanasiou Meropi, Wu Jane Y, Oppenheim Joost J, Yang De
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, 1050 Boyles Street, Frederick, MD 21702, USA.
J Immunol. 2004 Nov 15;173(10):5914-7. doi: 10.4049/jimmunol.173.10.5914.
Drm/Gremlin and Dan, two homologous secreted antagonists 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.
Drm/Gremlin和Dan是骨形态发生蛋白的两种同源分泌拮抗剂，已被证明可调节早期发育、肿瘤发生和肾脏病理生理学。在本研究中，我们报告Drm和Dan在物理和功能上与Slit1和Slit2蛋白相互作用。Drm与Slits的结合取决于其糖基化，且不受骨形态发生蛋白的干扰。重要的是，Drm和Dan作为基质细胞衍生因子1α（SDF-1α）或fMLP诱导的单核细胞迁移的抑制剂。Dan对SDF-1α诱导的单核细胞趋化作用的抑制并非由于阻断SDF-1α与其受体的结合。因此，结果表明Drm和Dan可与Slit蛋白相互作用并作为单核细胞趋化作用的抑制剂，证明了这些蛋白以前未被识别的生物学作用。
