Characterization of a 150 kDa accessory receptor for TGF-beta 1 on keratinocytes : direct evidence for a GPI anchor and ligand binding of the released form.

Authors: Tam, Betty Y. Y.; Larouche, DanielleGermain, Lucie; Hooper, N.M; Philip, Anie
Other Title(s): Characterization of a 150 kDa accessory receptor for TGF-β1 on keratinocytes : direct evidence for a GPI anchor and ligand binding of the released form.
Abstract: Fibroblasts play a critical role in wound repair and in the development of fibrotic diseases, and transforming growth factor-β (TGF-β) has been shown to profoundly modulate fibroblast function. However, there is limited information on the TGF-β receptor types, isoform specificity, and complex formation in skin fibroblasts. Here, we report that normal adult human skin fibroblasts display two isoform-specific, cell surface glycosyl phosphatidylinositol (GPI)-anchored, TGF-β binding proteins in addition to the type I, II, and III TGF-β receptors. The identities of these proteins are confirmed on the basis of their affinity for TGF-β isoforms, immunoprecipitation with specific antireceptor antibodies, and other biochemical analyses. Immunoprecipitation results also indicated oligomeric complex formation between type I and II and between type II and III TGF-β receptors. Furthermore, by using affinity labeling and two-dimensional electrophoresis, we demonstrate the occurrence of type I and II heterodimers and type I homodimers of TGF-β receptors on these cells. Because the type I receptor does not bind TGF-β in the absence of type II receptor, these results indicate that one molecule of TGF-β induces the formation of a heterooligomeric complex containing more than one molecule each of type I and II TGF-β receptors on these cells. These cells respond to TGF-β by markedly down-regulating all five binding proteins and by potently augmenting DNA synthesis. These results allow the expansion of the proposed heteromeric TGF-β receptor signaling paradigm using mutantcells that are unresponsive to TGF-β and cell lines that have been transfected to overexpress these receptors, to include normal TGF-β-responsive cells. In addition, the definition of TGF-β receptor profiles in human skin fibroblasts provides important information for studying their alterations in these cells in various skin diseases.
Document Type: Article de recherche
Issue Date: 5 September 2001
Open Access Date: Restricted access
Document version: VoR
This document was published in: Journal of cellular biochemistry, Vol. 83 (3), 494-507 (2001)
Alternative version: 10.1002/jcb.1074
Collection:Articles publiés dans des revues avec comité de lecture

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