JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wells, R. G.
Right arrow Articles by Lodish, H. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wells, R. G.
Right arrow Articles by Lodish, H. F.

J Biol Chem, Vol. 274, Issue 9, 5716-5722, February 26, 1999

Transforming Growth Factor-beta Induces Formation of a Dithiothreitol-resistant Type I/Type II Receptor Complex in Live Cells

Rebecca G. Wellsab, Lilach Gilboae, Yin Sunb, Xuedong Liub, Yoav I. Henise, and Harvey F. Lodishbi

From b The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, e Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel, a Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, and i Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Transforming growth factor-beta (TGF-beta ) binds to and signals via two serine-threonine kinase receptors, the type I (Tbeta RI) and type II (Tbeta RII) receptors. We have used different and complementary techniques to study the physical nature and ligand dependence of the complex formed by Tbeta RI and Tbeta RII. Velocity centrifugation of endogenous receptors suggests that ligand-bound Tbeta RI and Tbeta RII form a heteromeric complex that is most likely a heterotetramer. Antibody-mediated immunofluorescence co-patching of epitope-tagged receptors provides the first evidence in live cells that Tbeta RI·Tbeta RII complex formation occurs at a low but measurable degree in the absence of ligand, increasing significantly after TGF-beta binding. In addition, we demonstrate that pretreatment of cells with dithiothreitol, which inhibits the binding of TGF-beta to Tbeta RI, does not prevent formation of the Tbeta RI·Tbeta RII complex, but increases its sensitivity to detergent and prevents TGF-beta -activated Tbeta RI from phosphorylating Smad3 in vitro. This indicates that either a specific conformation of the Tbeta RI·Tbeta RII complex, disrupted by dithiothreitol, or direct binding of TGF-beta to Tbeta RI is required for signaling.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 ReproductionHome page
S J. Lin, T. F Lerch, R. W Cook, T. S Jardetzky, and T. K Woodruff
The structural basis of TGF-{beta}, bone morphogenetic protein, and activin ligand binding.
Reproduction, August 1, 2006; 132(2): 179 - 190.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. S. Siddiqui, Z. K. Siddiqui, and A. B. Malik
Albumin endocytosis in endothelial cells induces TGF-{beta} receptor II signaling
Am J Physiol Lung Cell Mol Physiol, May 1, 2004; 286(5): L1016 - L1026.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
S. Hayes, A. Chawla, and S. Corvera
TGF{beta} receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2
J. Cell Biol., September 29, 2002; 158(7): 1239 - 1249.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Gent, P. van Kerkhof, M. Roza, G. Bu, and G. J. Strous
Ligand-independent growth hormone receptor dimerization occurs in the endoplasmic reticulum and is required for ubiquitin system-dependent endocytosis
PNAS, July 23, 2002; 99(15): 9858 - 9863.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. G. Penheiter, H. Mitchell, N. Garamszegi, M. Edens, J. J. E. Dore Jr., and E. B. Leof
Internalization-Dependent and -Independent Requirements for Transforming Growth Factor {beta} Receptor Signaling via the Smad Pathway
Mol. Cell. Biol., July 1, 2002; 22(13): 4750 - 4759.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. V. Parekh, P. Gama, X. Wen, R. Demopoulos, J. S. Munger, M.-L. Carcangiu, M. Reiss, and L. I. Gold
Transforming Growth Factor {beta} Signaling Is Disabled Early in Human Endometrial Carcinogenesis Concomitant with Loss of Growth Inhibition
Cancer Res., May 1, 2002; 62(10): 2778 - 2790.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
F Biasi, L Tessitore, D Zanetti, J C Cutrin, B Zingaro, E Chiarpotto, N Zarkovic, G Serviddio, and G Poli
Associated changes of lipid peroxidation and transforming growth factor {beta}1 levels in human colon cancer during tumour progression
Gut, March 1, 2002; 50(3): 361 - 367.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Nohe, S. Hassel, M. Ehrlich, F. Neubauer, W. Sebald, Y. I. Henis, and P. Knaus
The Mode of Bone Morphogenetic Protein (BMP) Receptor Oligomerization Determines Different BMP-2 Signaling Pathways
J. Biol. Chem., February 8, 2002; 277(7): 5330 - 5338.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. N. Constantinescu, T. Keren, M. Socolovsky, H.-s. Nam, Y. I. Henis, and H. F. Lodish
Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain
PNAS, April 10, 2001; 98(8): 4379 - 4384.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. A. Harrison, P. G. Farnworth, K. L. Chan, P. G. Stanton, G. T. Ooi, J. K. Findlay, and D. M. Robertson
Identification of Specific Inhibin A-Binding Proteins on Mouse Leydig (TM3) and Sertoli (TM4) Cell Lines
Endocrinology, April 1, 2001; 142(4): 1393 - 1402.
[Abstract] [Full Text]

Home page
 J. Cell Sci.Home page
M Ehrlich, A Shmuely, and Y. Henis
A single internalization signal from the di-leucine family is critical for constitutive endocytosis of the type II TGF-(&bgr;) receptor
J. Cell Sci., January 5, 2001; 114(9): 1777 - 1786.
[Abstract] [PDF]

Home page
 Mol. Biol. CellHome page
L. Gilboa, A. Nohe, T. Geissendörfer, W. Sebald, Y. I. Henis, and P. Knaus
Bone Morphogenetic Protein Receptor Complexes on the Surface of Live Cells: A New Oligomerization Mode for Serine/Threonine Kinase Receptors
Mol. Biol. Cell, March 1, 2000; 11(3): 1023 - 1035.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
H.-J. Zhu, J. Iaria, and A. M. Sizeland
Smad7 Differentially Regulates Transforming Growth Factor beta -mediated Signaling Pathways
J. Biol. Chem., November 5, 1999; 274(45): 32258 - 32264.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-J. Zhu and A. M. Sizeland
Extracellular Domain of the Transforming Growth Factor-beta Receptor Negatively Regulates Ligand-independent Receptor Activation
J. Biol. Chem., October 8, 1999; 274(41): 29220 - 29227.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Razani, X. L. Zhang, M. Bitzer, G. von Gersdorff, E. P. Bottinger, and M. P. Lisanti
Caveolin-1 Regulates Transforming Growth Factor (TGF)-beta /SMAD Signaling through an Interaction with the TGF-beta Type I Receptor
J. Biol. Chem., February 23, 2001; 276(9): 6727 - 6738.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Keren, M. G. Roth, and Y. I. Henis
Internalization-competent Influenza Hemagglutinin Mutants Form Complexes with Clathrin-deficient Multivalent AP-2 Oligomers in Live Cells
J. Biol. Chem., July 20, 2001; 276(30): 28356 - 28363.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.