56 research outputs found
Transforming growth factor (TGF)-beta 1 internalization: modulation by ligand interaction with TGF-beta receptors types I and II and a mechanism that is distinct from clathrin-mediated endocytosis
Transforming growth factor-β (TGF-β) internalization was studied by monitoring the uptake of125I-TGF-β1 in Mv1Lu cells, which endogenously express TGF-β receptors types I (RI), II (RII), and III (RIII), and 293 cells transfected with RI and RII. At 37 °C internalization occurred rapidly, within 10 min of ligand addition. Internalization was optimal in 293 cells expressing both RI and RII. Internalization was prevented by phenylarsine oxide, a nonspecific inhibitor of receptor internalization, but was not affected by reagents that interfere with clathrin-mediated endocytosis such as monodansylcadaverine, K44A dynamin, and inhibitors of endosomal acidification. Electron microscopic examination of Mv1Lu cells treated with 125I- TGF-β1 at 37 °C indicated that internalization occurred via a noncoated vesicular mechanism. Internalization was prevented by prebinding cells with TGF-β1 at 4 °C for 2 h prior to switching the cells to 37 °C. This was attributed to a loss of receptor binding, as indicated by a rapid decrease in the amount of TGF-β1 bound to the cell surface at 37 °C and by a reduction in the labeling intensities of RI and RII in125I-TGF-β1-cross-linking experiments. Mv1Lu or 293 (RI+RII) cells, prebound with TGF-β1 at 4 °C and subsequently stripped of ligand by an acid wash, nevertheless initiated a signaling response upon transfer to 37 °C, suggesting that prebinding promotes formation of stable RI·RII complexes that can signal independently of ligand
Identification of high-quality cancer prognostic markers and metastasis network modules
There has been great interest in attempting to
identify gene expression signatures that predict cancer survival. In this study a new
algorithm is developed to analyse gene expression datasets that accurately classify both ER+
and ER− breast cancers into low- and high-risk groups
Interaction of transforming growth factor-beta 1 with alpha 2-macroglobulin. Role in transforming growth factor-beta 1 clearance.
It has been widely assumed that the interaction of transforming growth factor-beta 1 (TGF-beta 1) with its serum-binding protein, alpha 2-macroglobulin (alpha 2M), mediates the rapid clearance of TGF-beta 1 from the circulation. To test this, we have analyzed the effect of TGF-beta 1 binding on the conformational state of alpha 2M. Our results demonstrate that the binding of TGF-beta 1 to alpha 2M does not lead to the conformational change in the alpha 2M molecule that is required for the clearance of the alpha 2M.TGF-beta 1 complex via the alpha 2M receptor. Furthermore, endogenous TGF-beta 1 is associated with the conformationally unaltered slow clearance form of alpha 2M. Clearance studies in mice show that the half-life of 125I-TGF-beta 1 in the circulation (1.6 +/- 0.71 min) is not affected by blocking the alpha 2M receptor with excess conformationally altered alpha 2M. These results suggest that TGF-beta 1 is rapidly cleared from the circulation after injection by a pathway not involving alpha 2M
Predominant intracellular localization of the type I transforming growth factor-beta receptor and increased nuclear accumulation after growth arrest
NRC publication: Ye
Down-regulation of transforming growth factor-beta receptors: cooperativity between the types I, II, and III receptors and modulation at the cell surface
UI - 99458858NRC publication: Ye
Binding of transforming growth factor-beta (TGF-beta) to pregnancy zone protein (PZP). Comparison to the TGF-beta-alpha 2-macroglobulin interaction
Peer reviewed: YesNRC publication: Ye
Mapping of the ligand binding domain of the transforming growth factor beta receptor type III by deletion mutagenesis
NRC publication: Ye
Purification of the extracellular domain of the epidermal growth factor receptor produced by recombinant baculovirus-infected insect cells in a 10-L reactor
NRC publication: Ye
Mapping of putative binding sites on the ectodomain of the type II TGF-beta receptor by scanning-deletion mutagenesis and knowledge-based modeling
UI - 99379603NRC publication: Ye
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