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Characterization of a 60-kDa cell surface-associated transforming growth factor-β binding protein that can interfere with transforming growth factor-β receptor binding

✍ Scribed by Ester Piek; Petra Franzèn; Carl-Henrik Heldin; Peter Ten Dijke


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
419 KB
Volume
173
Category
Article
ISSN
0021-9541

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✦ Synopsis


We have characterized a 60-kDa transforming growth factor-b (TGF-b) binding protein that was originally identified on LNCaP adenocarcinoma prostate cells by affinity cross-linking of cell surface proteins by using 125 I-TGF-b1. Binding of 125 I-TGF-b1 to the 60-kDa protein was competed by an excess of unlabeled TGF-b1 but not by TGF-b2, TGF-b3, activin, or osteogenic protein-1 (OP-1), also termed bone morphogenetic protein-7 (BMP-7). In addition, no binding of 125 I-TGF-b2 and 125 I-TGF-b3 to the 60-kDa binding protein on LNCaP cells could be demonstrated by using affinity labeling techniques. The 60-kDa TGF-b binding protein showed no immunoreactivity with antibodies against the known type I and type II receptors for members of the TGF-b superfamily. Treatment of LNCaP cells with 0.25 M NaCl, 1 mg/ml heparin, or 10% glycerol caused a release of the 60-kDa protein from the cell surface. In addition, we found that the previously described TGF-b type IV receptor on GH3 cells, which does not form a heteromeric complex with TGF-b receptors, could be released from the cell surface by these same treatments. This suggests that the 60-kDa protein and the similarly sized TGF-b type IV receptor are related proteins. The eluted 60-kDa LNCaP protein was shown to interfere with the binding of TGF-b to the TGF-b receptors. Thus, the cell surface-associated 60-kDa TGF-b binding protein may play a role in regulating TGF-b binding to TGF-b receptors.