Heteromeric and homomeric transforming growth factor-beta receptors show distinct signaling and endocytic responses in epithelial cells - PubMed

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• PMID: 9822641
• DOI: 10.1074/jbc.273.48.31770

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Heteromeric and homomeric transforming growth factor-beta receptors show distinct signaling and endocytic responses in epithelial cells

J J Doré Jr et al. J Biol Chem. 1998.

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Abstract

Transforming growth factor-beta (TGF-beta) induces distinct responses dependent upon the cellular context. It is unclear whether the initial receptor interactions identified in one cell type will be operative in another. Utilizing a chimeric receptor strategy we have examined the signaling and endocytic activity of both heteromeric (type I/type II) and homomeric (type I/type I or type II/type II) TGF-betaR interactions in Mv1Lu epithelial cells. In agreement with that observed in mesenchymal cells, all TGF-betaR signaling in Mv1Lu cells required the formation of a heteromeric type I-type II receptor complex. However, the initial endocytic response to TGF-betaR oligomerization was distinctly regulated in the two cell types. While heteromeric TGF-beta receptors were internalized and down-regulated, homomeric TGF-betaR interactions showed diminished endocytic activity in Mv1Lu cells. This contrasts to that observed in mesenchymal cultures where ligand bound to TGF-betaR homomers was internalized, yet the receptors were not down-regulated. Moreover, while previous reports have suggested that mutations at serine 172 or threonine 176 in the type I TGF-betaR separated transcriptional from proliferative responses, we found no separation of pathways or effect on initial endocytic activity when the analogous mutations were made in the chimeric receptors.

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