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PMID:15975920

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Citation

Babitt, JL, Zhang, Y, Samad, TA, Xia, Y, Tang, J, Campagna, JA, Schneyer, AL, Woolf, CJ and Lin, HY (2005) Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor. J. Biol. Chem. 280:29820-7

Abstract

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGF-beta) superfamily of ligands, which regulate many mammalian physiologic and pathophysiologic processes. BMPs exert their effects through type I and type II serine/threonine kinase receptors and the Smad intracellular signaling pathway. Recently, the glycosylphosphatidylinositol (GPI)-anchored protein DRAGON was identified as a co-receptor for BMP signaling. Here, we investigate whether a homologue of DRAGON, repulsive guidance molecule (RGMa), is similarly involved in the BMP signaling pathway. We show that RGMa enhances BMP, but not TGF-beta, signals in a ligand-dependent manner in cell culture. The soluble extracellular domain of RGMa fused to human Fc (RGMa.Fc) forms a complex with BMP type I receptors and binds directly and selectively to radiolabeled BMP-2 and BMP-4. RGMa mediates BMP signaling through the classical BMP signaling pathway involving Smad1, 5, and 8, and it up-regulates endogenous inhibitor of differentiation (Id1) protein, an important downstream target of BMP signals. Finally, we demonstrate that BMP signaling occurs in neurons that express RGMa in vivo. These data are consistent with a role for RGMa as a BMP co-receptor.

Links

PubMed Online version:10.1074/jbc.M503511200

Keywords

Amino Acid Sequence; Animals; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins/physiology; Cells, Cultured; DNA-Binding Proteins/physiology; GPI-Linked Proteins; Humans; Mice; Molecular Sequence Data; Nerve Tissue Proteins/physiology; Phosphoproteins/physiology; Rats; Receptors, Growth Factor/physiology; Signal Transduction; Smad Proteins; Smad1 Protein; Smad5 Protein; Smad8 Protein; Spinal Cord/metabolism; Trans-Activators/physiology; Transforming Growth Factor beta/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BMP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6PCX7

F

Seeded From UniProt

complete

MOUSE:BMP4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6PCX7

F

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RGMA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P21274
PR:P21275

F

Seeded From UniProt

complete

MOUSE:RGMA

acts_upstream_of_or_within

GO:0030509: BMP signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88177
MGI:MGI:88181

P

Seeded From UniProt

complete

MOUSE:RGMA

enables

GO:0015026: coreceptor activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88177
MGI:MGI:88180

F

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0030509: BMP signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2679262

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0030509: BMP signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2679262

P

Seeded From UniProt

complete


See also

References

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