TY - JOUR
T1 - Heteromeric and homomeric transforming growth factor-β receptors show distinct signaling and endocytic responses in epithelial cells
AU - Doré, Jules J.E.
AU - Edens, Maryanne
AU - Garamszegi, Nandor
AU - Leof, Edward B.
PY - 1999/11/27
Y1 - 1999/11/27
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.273.48.31770
DO - 10.1074/jbc.273.48.31770
M3 - Article
C2 - 9822641
AN - SCOPUS:0033610860
SN - 0021-9258
VL - 273
SP - 31770
EP - 31777
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -