Abstract |
Transforming growth factor (TGF)-beta1 is secreted as a latent form, which consists of its mature form and a latency-associated peptide (beta1-LAP) in either the presence or the absence of additional latent TGF-beta1-binding protein. We recently reported that three different missense mutations (R218H, R218C, and C225R) of beta1-LAP cause the Camurati-Engelmann disease (CED), an autosomal dominant disorder characterized by hyperosteosis and sclerosis of the diaphysis of the long bones. Pulse-chase experiments using fibroblasts from CED patients and expression experiments of the mutant genes in an insect cell system suggest that these mutations disrupt the association of beta1-LAP and TGF-beta1 and the subsequent release of the mature TGF-beta1. Furthermore, the cell growth of fibroblasts from a CED patient and mutant gene-transfected fibroblasts was suppressed via TGF-beta1. The growth suppression observed was attenuated by neutralizing antibody to TGF-beta1 or by treatment of dexamethasone. On the other hand, the proliferation of human osteoblastic MG-63 cells was accelerated by coculture with CED fibroblasts. These data suggest that the domain-specific mutations of beta1-LAP result in a more facile activation of TGF-beta1, thus causing CED.
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Authors | T Saito, A Kinoshita, Yoshiura Ki, Y Makita, K Wakui, K Honke, N Niikawa, N Taniguchi |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 276
Issue 15
Pg. 11469-72
(Apr 13 2001)
ISSN: 0021-9258 [Print] United States |
PMID | 11278244
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Peptide Fragments
- Protein Precursors
- Recombinant Proteins
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
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Topics |
- Camurati-Engelmann Syndrome
(genetics, metabolism)
- Cell Division
- Cell Line
- Humans
- Mutation
- Peptide Fragments
(genetics)
- Protein Precursors
(genetics)
- Recombinant Proteins
(genetics)
- Transfection
- Transforming Growth Factor beta
(biosynthesis)
- Transforming Growth Factor beta1
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