CHARACTERIZATION AND CLONING OF A RECEPTOR FOR BMP-2 AND BMP-4 FROM NIH 3T3 CELLS

被引:317
作者
KOENIG, BB
COOK, JS
WOLSING, DH
TING, J
TIESMAN, JP
CORREA, PE
OLSON, CA
PECQUET, AL
VENTURA, FS
GRANT, RA
CHEN, GX
WRANA, JL
MASSAGUE, J
ROSENBAUM, JS
机构
[1] PROCTER & GAMBLE CO, DIV CORP RES, MIAMI VALLEY LABS, CINCINNATI, OH 45239 USA
[2] MEM SLOAN KETTERING CANC CTR, CELL BIOL & GENET PROGRAM, NEW YORK, NY 10021 USA
[3] MEM SLOAN KETTERING CANC CTR, HOWARD HUGHES MED INST, NEW YORK, NY 10021 USA
关键词
D O I
10.1128/MCB.14.9.5961
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The bone morphogenetic proteins (BMPs) are a group of transforming growth factor beta (TGF-beta)-related factors whose only receptor identified to date is the product of the daf-4 gene from Caenorhabditis elegans. Mouse embryonic NIH 3T3 fibroblasts display high-affinity (125I)-BMP-4 binding sites. Binding assays are not possible with the isoform I-125-BMP-2 unless the positively charged N-terminal sequence is removed to create a modified BMP-2, I-125-DR-BMP-2. Cross-competition experiments reveal that BMP-2 and BMP-4 interact with the same binding sites. Affinity cross-linking assays show that both BMPs interact with cell surface proteins corresponding in size to the type I (57- to 62-kDa) and type II (75- to 82-kDa) receptor components for TGF-P and activin. Using a PCR approach, we have cloned a cDNA from NIH 3T3 cells which encodes a novel member of the transmembrane serine/threonine kinase family most closely resembling the cloned type I receptors for TGF-P and activin. Transient expression of this receptor in COS-7 cells leads to an increase in specific I-125-BMP-4 binding and the appearance of a major affinity-labeled product of similar to 64 kDa that can be labeled by either tracer. This receptor has been named BRK-1 in recognition of its ability to bind BMP-2 and BMP-4 and its receptor kinase structure. Although BRK-1 does not require cotransfection of a type II receptor in order to bind ligand in COS cells, complex: formation between BRK-1 and the BMP type II receptor DAF-4 can be demonstrated when the two receptors are eoexpressed, affinity labeled, and immunoprecipitated with antibodies to either receptor subunit. We conclude that BRK-1 is a putative BMP type I receptor capable of interacting with a known type II receptor for BMPs.
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收藏
页码:5961 / 5974
页数:14
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