TY - JOUR
T1 - Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis
AU - Hoang, Bang
AU - Moos, Malcolm
AU - Vukicevic, Slobodan
AU - Luyten, Frank P.
PY - 1996
Y1 - 1996
N2 - Articular cartilage extracts were prepared to characterize protein fractions with in vivo chondrogenic activity (Chang, S., Hoang, B., Thomas, J. T., Vukicevic, S., Luyten, F. P., Ryba, N. J. P., Kozak, C. A., Reddi, A. H., and Moos, M. (1994) J. Biol. Chem. 269, 28227-28234). Trypsin digestion of highly purified chondrogenic protein fractions allowed the identification of several unique peptides by amino acid sequencing. We discovered a novel cDNA encoding a deduced 36-kDa protein by using degenerate oligonucleotide primers derived from a 30-residue peptide in reverse transcription polymerase chain reactions. Its N.terminal domain showed ≃50% amino acid identity to the corresponding region of the Drosophila gene frizzled, which has been implicated in the specification of hair polarity during development. Hydropathy and structural analyses of the open reading frame revealed the presence of a signal peptide and a hydrophobic domain followed by multiple potential serine/threonine phosphorylation sites and a serine-rich C terminus. Cell fractionation studies of primary bovine articular chondrocytes and transfected COS cells suggested that the protein is membrane-associated. In situ hybridization and immunostaining of human embryonic sections demonstrated predominant expression surrounding the chondrifying bone primordia and subsequently in the chondrocytes of the epiphyses in a graded distribution that decreased toward the primary ossification center. Transcripts were present in the craniofacial structures but not in the vertebral bodies. Because it is expressed primarily in the cartilaginous cores of developing long bones during embryonic and fetal development (6-13 weeks) and is homologous to the polarity-determining gene frizzled, we believe that this gene, which we named frzb, is involved in morphogenesis of the mammalian skeleton.
AB - Articular cartilage extracts were prepared to characterize protein fractions with in vivo chondrogenic activity (Chang, S., Hoang, B., Thomas, J. T., Vukicevic, S., Luyten, F. P., Ryba, N. J. P., Kozak, C. A., Reddi, A. H., and Moos, M. (1994) J. Biol. Chem. 269, 28227-28234). Trypsin digestion of highly purified chondrogenic protein fractions allowed the identification of several unique peptides by amino acid sequencing. We discovered a novel cDNA encoding a deduced 36-kDa protein by using degenerate oligonucleotide primers derived from a 30-residue peptide in reverse transcription polymerase chain reactions. Its N.terminal domain showed ≃50% amino acid identity to the corresponding region of the Drosophila gene frizzled, which has been implicated in the specification of hair polarity during development. Hydropathy and structural analyses of the open reading frame revealed the presence of a signal peptide and a hydrophobic domain followed by multiple potential serine/threonine phosphorylation sites and a serine-rich C terminus. Cell fractionation studies of primary bovine articular chondrocytes and transfected COS cells suggested that the protein is membrane-associated. In situ hybridization and immunostaining of human embryonic sections demonstrated predominant expression surrounding the chondrifying bone primordia and subsequently in the chondrocytes of the epiphyses in a graded distribution that decreased toward the primary ossification center. Transcripts were present in the craniofacial structures but not in the vertebral bodies. Because it is expressed primarily in the cartilaginous cores of developing long bones during embryonic and fetal development (6-13 weeks) and is homologous to the polarity-determining gene frizzled, we believe that this gene, which we named frzb, is involved in morphogenesis of the mammalian skeleton.
UR - http://www.scopus.com/inward/record.url?scp=0029959105&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029959105&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.42.26131
DO - 10.1074/jbc.271.42.26131
M3 - Article
C2 - 8824257
AN - SCOPUS:0029959105
SN - 0021-9258
VL - 271
SP - 26131
EP - 26137
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -