TGF-beta receptor expression on human keratinocytes : a 150 kDa GPI-anchored TGF-beta1 binding protein forms a heteromeric complex with type I and type II receptors

Authors: Tam, Betty Y. Y.; Germain, Lucie; Philip, Anie
Other Title(s): TGF-β receptor expression on human keratinocytes : a 150 kDa GPI-anchored TGF-β1 binding protein forms a heteromeric complex with type I and type II receptors
Abstract: Keratinocytes play a critical role in re-epithelialization during wound healing, and alterations in keratinocyte proliferation and function are associated with the development of various skin diseases. Although it is well documented that TGF-b has profound effects on keratinocyte growth and function, there is a paucity of information on the types, isoform specificity and complex formation of TGF-b receptors on keratinocytes. Here, we report that in addition to the types I, II, and III TGF-b receptors, early passage adult and neonatal human keratinocytes display a cell surface glycosylphosphatidylinositol (GPI)-anchored 150 kDa TGF-b1 binding protein. The identities of the four proteins were confirmed on the basis of their affinity for TGF-b isoforms, immunoprecipitation with specific anti-receptor antibodies, sensitivity to phosphatidylinositol specific phospholipase C and dithiothreitol, and 2-dimensional electrophoresis. Interestingly, the antitype I TGF-b receptor antibody immunoprecipitated not only the type I receptor, but also the type II receptor and the 150 kDa component, suggesting that the 150 kDa component form heteromeric complexes with the signalling receptors. In addition, two-dimensional (nonreducing/reducing) electrophoresis confirmed the occurrence of a heterotrimeric complex consisting of the 150 kDa TGF-b1 binding protein, the type II receptor, and the type I receptor. This technique also demonstrated the occurrence of types I and II heterodimers and type I homodimers of TGF-b receptors on keratinocytes, supporting the heterotetrameric model of TGF-b signalling proposed using mutant cells and cells transfected to overexpress these receptors. The keratinocytes responded to TGF-b by markedly downregulating all four TGF-b binding proteins and by potently inhibiting DNA synthesis. The demonstration that the 150 kDa GPI-anchored TGF-b1 binding protein forms a heteromeric complex with the TGF-b signalling receptors suggests that this GPI-anchored protein may modify TGF-b signalling in human keratinocytes
Document Type: Article de recherche
Issue Date: 15 September 1998
Open Access Date: Restricted access
Document version: VoR
This document was published in: Journal of cellular biochemistry, Vol. 70 (4),573-586 (1998);2-I/full
Alternative version: 10.1002/(SICI)1097-4644(19980915)
Collection:Articles publiés dans des revues avec comité de lecture

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