Heteromeric and Homomeric Transforming Growth Factor-β Receptors Show Distinct Signaling and Endocytic Responses in Epithelial Cells*
- From the Thoracic Disease Research Unit and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905
Abstract
Transforming growth factor-β (TGF-β) 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-βR interactions in Mv1Lu epithelial cells. In agreement with that observed in mesenchymal cells, all TGF-βR signaling in Mv1Lu cells required the formation of a heteromeric type I-type II receptor complex. However, the initial endocytic response to TGF-βR oligomerization was distinctly regulated in the two cell types. While heteromeric TGF-β receptors were internalized and down-regulated, homomeric TGF-βR interactions showed diminished endocytic activity in Mv1Lu cells. This contrasts to that observed in mesenchymal cultures where ligand bound to TGF-βR 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-βR 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.
Footnotes
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↵* This work was supported by Grants GM-54200 and GM-55816 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Guggenheim 6, Mayo Clinic, Rochester, MN 55905. Tel.: 507-284-5717; Fax: 507-284-4521; E-mail: leof.edward{at}mayo.edu.
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↵2 J. J. E. Doré Jr., M Edens, N. Garamszegi, and E. B. Leof, unpublished data.
- Abbreviations:
- TGF-β
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transforming growth factor-β
- GM-CSF
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granulocyte macrophage-colony stimulating factor
- FBS
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fetal bovine serum
- DMEM
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Dulbecco’s modified Eagle’s medium
- FACS
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fluorescence-activated cell sorter.
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- Received May 15, 1998.
- Revision received July 29, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
