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

Jules J.E. Doré, Maryanne Edens, Nandor Garamszegi, Edward B. Leof

Research output: Contribution to journalArticle

42 Scopus citations

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 17G 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.

Original languageEnglish (US)
Pages (from-to)31770-31777
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number48
DOIs
StatePublished - Nov 27 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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