Cutting edge: bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with Slits and act as negative regulators of monocyte chemotaxis.
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.
Chen
Bo
B
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, 1050 Boyles Street, Frederick, MD 21702, USA.
Blair
Donald G
DG
Plisov
Sergei
S
Vasiliev
Gennady
G
Perantoni
Alan O
AO
Chen
Qian
Q
Athanasiou
Meropi
M
Wu
Jane Y
JY
Oppenheim
Joost J
JJ
Yang
De
D
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D018797:Cell Cycle Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D020798:Two-Hybrid System Techniques; D000098552:Slit Homolog 2 Protein
D019485:Bone Morphogenetic Proteins; D018797:Cell Cycle Proteins; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C490087:NBL1 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; C492289:SLIT1 protein, human; D000098552:Slit Homolog 2 Protein