A fibroblast chondroitin sulfate proteoglycan core protein contains lectin-like and growth factor-like sequences.
We have isolated cDNA clones that code for a proteoglycan-related polypeptide with unique properties. A lambda gt11 expression library made from human fibroblast mRNA was screened with an antiserum made against a proteoglycan fraction from human fetal membranes. One group of positive clones revealed an open reading frame coding for 685 amino acids from the COOH terminus of a polypeptide. This amino acid sequence contains a domain that is strongly homologous with the COOH-terminal core protein domain of the large aggregating cartilage proteoglycan. This domain also contains sequences that are homologous with vertebrate lectins that bind terminal galactosyl, N-acetyl-glucosaminyl or mannosyl residues. On the NH2-terminal side of the lectin-like domain the cDNA-derived amino acid sequence contains two epidermal growth factor-related segments. The cDNA clones were shown to belong to a chondroitin sulfate proteoglycan by using antisera made against two peptides predicted from the cDNA sequence. These antisera were reactive with a proteoglycan fraction from fibroblasts after chondroitinase treatment of the fraction but not after treatment with heparinase or no treatment. Among the several polypeptides reactive with the anti-peptide antibodies the largest one, corresponding to a molecular weight of about 400,000, is likely to be the intact core protein, whereas the smaller polypeptides may be processing products or products of artifactual proteolysis. These results show that the amino acid sequence belongs to a proteoglycan core protein, and the sequence, therefore, provides a molecular definition to this proteoglycan. The lectin-related and growth factor-like sequences in the core protein of this proteoglycan suggest that it may play a role in intercellular signaling.
Krusius
T
T
Cancer Research Center, La Jolla Cancer Research Foundation, California 92037.
Gehlsen
K R
KR
Ruoslahti
E
E
D053674:Aggrecans; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification; D004262:DNA Restriction Enzymes; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics*; D006133:Growth Substances; D006801:Humans; D037102:Lectins; D037181:Lectins, C-Type; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006133:Growth Substances; D037102:Lectins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D004247:DNA; D004262:DNA Restriction Enzymes