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Transforming growth factor‐β receptor expression on human skin fibroblasts: Dimeric complex formation of type I and type II receptors and identification of glycosyl phosphatidylinositol‐anchored transforming growth factor‐β binding proteins
Author(s) -
Tam Betty Y. Y.,
Philip Anie
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199809)176:3<553::aid-jcp12>3.0.co;2-0
Subject(s) - transforming growth factor , receptor , growth factor , microbiology and biotechnology , identification (biology) , growth factor receptor , chemistry , tgf alpha , phosphatidylinositol , fibroblast growth factor receptor 4 , biology , biochemistry , signal transduction , fibroblast growth factor receptor , fibroblast growth factor , botany
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. J. Cell. Physiol. 176:553–564, 1998. © 1998 Wiley‐Liss, Inc.