Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1.
Bone morphogenetic protein-1 (BMP-1), a metalloprotease isolated from osteogenic extracts of demineralized bone, is capable of cleaving the C-propeptides of procollagen types I, II, and III. A single mammalian gene produces alternatively spliced RNA transcripts for BMP-1 and for a second longer protein, designated mammalian tolloid (mTld) due to a domain structure identical to that of the Drosophila dorsal-ventral patterning gene product tolloid (Tld). Here we report the use of a cDNA library, prepared from BMP-1/mTld-null mouse embryos, to isolate cDNA clones for a novel mammalian protein with a domain structure identical to that of mTld. The new protein, designated mammalian tolloid-like (mTll), has 76% identity with mTld for amino acid residues in all domains downstream of, and including, the protease domain. In contrast, the N-terminal activation domains of the two proteins show little similarity. In situ hybridizations show the distribution of mTll RNA to overlap extensively that previously shown for the BMP-1 and mTld RNA forms. However, mTll shows additional strong expression in structures of the developing, neonatal, and adult brain in which expression of BMP-1 and mTld has not been observed. The murine mTll gene (Tll) is mapped to central chromosome 8, which is a different chromosomal location than that of the BMP-1/mTld gene. Loci for some developmental abnormalities map to the same general chromosomal location as Tll.
Takahara
K
K
Department of Pathology, University of Wisconsin Medical School, Madison, Wisconsin, 53706, USA.
Brevard
R
R
Hoffman
G G
GG
Suzuki
N
N
Greenspan
D S
DS
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000737:chemistry*; D002874:Chromosome Mapping; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D015870:Gene Expression; D015723:Gene Library; D006133:Growth Substances / Q000737:chemistry*; D017403:In Situ Hybridization; D008322:Mammals; D008666:Metalloendopeptidases; D045726:Metalloproteases; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D055394:Tolloid-Like Metalloproteinases; D014158:Transcription, Genetic
D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D006133:Growth Substances; D011506:Proteins; D045726:Metalloproteases; D055394:Tolloid-Like Metalloproteinases; D008666:Metalloendopeptidases; C484477:Tll1 protein, mouse; C097491:Tok protein, Drosophila; C525707:Bmp1 protein, mouse; D055395:Bone Morphogenetic Protein 1