scholarly journals Endocytosis of the Type III Transforming Growth Factor-β (TGF-β) Receptor through the Clathrin-independent/Lipid Raft Pathway Regulates TGF-β Signaling and Receptor Down-regulation

2008 ◽  
Vol 283 (50) ◽  
pp. 34808-34818 ◽  
Author(s):  
Elizabeth C. Finger ◽  
Nam Y. Lee ◽  
Hye-jin You ◽  
Gerard C. Blobe
Keyword(s):  
Growth Factor ◽  
Lipid Raft ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Down Regulation ◽  
Type Iii ◽  
Β Receptor

scholarly journals Transforming Growth Factor β Receptor Signaling and Endocytosis Are Linked through a COOH Terminal Activation Motif in the Type I Receptor

2001 ◽  
Vol 12 (9) ◽  
pp. 2881-2893 ◽  
Author(s):  
Nandor Garamszegi ◽  
Jules J. E. Doré ◽  
Sumedha G. Penheiter ◽  
Maryanne Edens ◽  
Diying Yao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Kinase Domain ◽  
Type I ◽  
Receptor Signaling ◽  
Down Regulation ◽  
Critical Function ◽  
Β Receptor

Transforming growth factor β (TGF-β) coordinates a number of biological events important in normal and pathophysiological growth. In this study, deletion and substitution mutations were used to identify receptor motifs modulating TGF-β receptor activity. Initial experiments indicated that a COOH-terminal sequence between amino acids 482–491 in the kinase domain of the type I receptor was required for ligand-induced receptor signaling and down-regulation. These 10 amino acids are highly conserved in mammalian, Xenopus, andDrosophila type I receptors. Although mutation or deletion of the region (referred to as the NANDOR BOX, for nonactivating non–down-regulating) abolishes TGF-β–dependent mitogenesis, transcriptional activity, type I receptor phosphorylation, and down-regulation in mesenchymal cultures, adjacent mutations also within the kinase domain are without effect. Moreover, a kinase-defective type I receptor can functionally complement a mutant BOX expressing type I receptor, documenting that when the BOX mutant is activated, it has kinase activity. These results indicate that the sequence between 482 and 491 in the type I receptor provides a critical function regulating activation of the TGF-β receptor complex.

scholarly journals Coronary Vessel Development Is Dependent on the Type III Transforming Growth Factor β Receptor

2007 ◽  
Vol 101 (8) ◽  
pp. 784-791 ◽  
Author(s):  
Leigh A. Compton ◽  
Dru A. Potash ◽  
Christopher B. Brown ◽  
Joey V. Barnett
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Coronary Vessel ◽  
Type Iii ◽  
Vessel Development ◽  
Β Receptor

Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-β signaling at the bipotent erythro-megakaryocytic progenitor stage

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2784-2795 ◽  
Author(s):  
Voahangy Randrianarison-Huetz ◽  
Benoit Laurent ◽  
Valérie Bardet ◽  
Gerard C. Blobe ◽  
François Huetz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Receptor Gene ◽  
Erythroid Differentiation ◽  
Transforming Growth Factor Β ◽  
Type Iii ◽  
Smad2 Phosphorylation ◽  
Proliferation And Differentiation ◽  
Direct Target ◽  
Β Receptor

Abstract Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis. Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis. We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors. We further identify in this cell population the type III transforming growth factor-β receptor gene, TGFBR3, as a direct target of Gfi-1B. Knockdown of Gfi-1B results in altered transforming growth factor-β (TGF-β) signaling as shown by the increase in Smad2 phosphorylation and its inability to associate to the transcription intermediary factor 1-γ (TIF1-γ). Because the Smad2/TIF1-γ complex is known to specifically regulate erythroid differentiation, we propose that, by repressing TGF-β type III receptor (TβRΙII) expression, Gfi-1B favors the Smad2/TIF1-γ interaction downstream of TGF-β signaling, allowing immature progenitors to differentiate toward the erythroid lineage.

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