scholarly journals Estrogen induces apoptosis in a rat prostatic adenocarcinoma: Association with an increased expression of TGF- β1 and its type-I and type-II receptors

1996 ◽  
Vol 67 (4) ◽  
pp. 573-579 ◽  
Author(s):  
Maréne Landström ◽  
Solveig Eklöv ◽  
Pascal Colosetti ◽  
Sten Nilsson ◽  
Jan-Erik Damber ◽  
...  
Keyword(s):  
Prostatic Adenocarcinoma ◽  
Type I ◽  
Type Ii ◽  
Tgf Β1

scholarly journals Transforming growth factor-β type-II receptor signalling: intrinsic/associated casein kinase activity, receptor interactions and functional effects of blocking antibodies

1996 ◽  
Vol 316 (1) ◽  
pp. 303-310 ◽  
Author(s):  
Frederick L. HALL ◽  
Paul D. BENYA ◽  
Silvia R. PADILLA ◽  
Denise CARBONARO-HALL ◽  
Richard WILLIAMS ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Human Osteosarcoma Cells ◽  
Receptor Interactions ◽  
Tgf Β1 ◽  
Pai 1

The transforming growth factor β (TGF-β) family of growth factors control proliferation, extracellular matrix synthesis and/ or differentiation in a wide variety of cells. However, the molecular mechanisms governing ligand binding, receptor oligomerization and signal transduction remain incompletely understood. In this study, we utilized a set of antibodies selective for the extracellular and intracellular domains of the TGF-β type-II receptor as probes to investigate the intrinsic kinase activity of this receptor and its physical association in multimeric complexes with type-I and type-III receptors. The type-II receptor immunoprecipitated from human osteosarcoma cells exhibited autophosphorylation and casein kinase activity that was markedly stimulated by polylysine yet was insensitive to heparin. Affinity cross-linking of 125I-TGF-β1 ligand to cellular receptors followed by specific immunoprecipitation demonstrated that type-II receptors form stable complexes with both type-I and type-III receptors expressed on the surfaces of both human osteosarcoma cells and rabbit chondrocytes. Pretreatment of the cultured cells with an antibody directed against a distinct extracellular segment of the type-II receptor (anti-TGF-β-IIR-NT) effectively blocked the 125I-TGF-β labelling of type-I receptors without preventing the affinity labelling of type-II or type-III receptors, indicating a selective disruption of the type-I/type-II hetero-oligomers. The anti-TGF-β-IIR-NT antibodies also blocked the TGF-β-dependent induction of the plasminogen activator inhibitor (PAI-1) promoter observed in mink lung epithelial cells. However, the same anti-TGF-β-IIR-NT antibodies did not prevent the characteristic inhibition of cellular proliferation by TGF-β1, as determined by [3H]thymidine incorporation into DNA. The selective perturbation of PAI-1 promoter induction versus cell-cycle-negative regulation suggests that strategic disruption of TGF-β type-I and -II receptor interactions can effectively alter specific cellular responses to TGF-β signalling.

scholarly journals Transdifferentiation of alveolar epithelial type II to type I cells is controlled by opposing TGF-β and BMP signaling

2013 ◽  
Vol 305 (6) ◽  
pp. L409-L418 ◽  
Author(s):  
Lan Zhao ◽  
Min Yee ◽  
Michael A. O'Reilly
Keyword(s):  
Gene Expression ◽  
Bmp Signaling ◽  
Specific Gene ◽  
Type I ◽  
Type Ii ◽  
Specific Gene Expression ◽  
Alveolar Epithelial ◽  
Basal Expression ◽  
Atii Cell ◽  
Tgf Β1

Alveolar epithelial type II (ATII) cells are essential for maintaining normal lung homeostasis because they produce surfactant, express innate immune proteins, and can function as progenitors for alveolar epithelial type I (ATI) cells. Although autocrine production of transforming growth factor (TGF)-β1 has been shown to promote the transdifferentiation of primary rat ATII to ATI cells in vitro, mechanisms controlling this process still remain poorly defined. Here, evidence is provided that Tgf-β1, - 2, - 3 mRNA and phosphorylated SMAD2 and SMAD3 significantly increase as primary cultures of mouse ATII cells transdifferentiate to ATI cells. Concomitantly, bone morphogenetic protein ( Bmp)-2 and -4 mRNA, and phosphorylated SMAD1/5/8 expression decrease. Exogenously supplied recombinant human TGF-β1 inhibited BMP signaling and enhanced transdifferentiation by promoting the loss of ATII cell-specific gene expression and weakly stimulating ATI cell-specific gene expression. On the other hand, exogenously supplied recombinant human BMP-4 inhibited TGF-β signaling and delayed transdifferentiation by inhibiting the gain in ATI cell-specific gene expression and weakly delaying the loss of ATII cell-specific gene expression. In mouse lung epithelial (MLE15) cells, small-interfering RNA (siRNA) knockdown of TGF-β receptor type-1 enhanced basal expression of ATII genes while siRNA RNA knockdown of BMP receptors type-1a and -1b enhanced basal expression of ATI genes. Together, these results suggest that the rate of ATII cell transdifferentiation is controlled by the opposing actions of BMP and TGF-β signaling that switch during the process of transdifferentiation.

TGF-β1 modulates EGF-stimulated phosphatidylinositol 3-kinase activity in human airway smooth muscle cells

1997 ◽  
Vol 273 (6) ◽  
pp. L1220-L1227 ◽  
Author(s):  
Vera P. Krymskaya ◽  
Rebecca Hoffman ◽  
Andrew Eszterhas ◽  
Vincenzo Ciocca ◽  
Reynold A. Panettieri
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Kinase Activity ◽  
Type I ◽  
Type Ii ◽  
Human Airway Smooth Muscle ◽  
S6 Kinase ◽  
Kinase Activation ◽  
P70 S6 Kinase ◽  
Tgf Β1

Regulation of phosphatidylinositol (PI) 3-kinase plays an important role in modulating cellular function. We have previously shown that transforming growth factor (TGF)-β1 inhibited epidermal growth factor (EGF)-induced human airway smooth muscle (hASM) cell proliferation and that PI 3-kinase activation is a necessary signaling event in mitogen-induced hASM cell growth. In this study, we postulated that TGF-β1 may modulate EGF-induced PI 3-kinase activation. To date, no study has examined the effects of TGF-β1 on PI 3-kinase activity. In cultured hASM cells, EGF induced a 5.7 ± 1.2-fold activation of PI 3-kinase compared with diluent-treated cells. Although TGF-β1 alone did not alter PI 3-kinase activation, TGF-β1 markedly enhanced EGF-induced PI 3-kinase activity, with a 16.6 ± 1.9-fold increase over control cells treated with diluent alone. EGF significantly increased the association of PI 3-kinase with tyrosine phosphorylated proteins, and TGF-β1 pretreatment before EGF stimulation apparently did not alter this association. Interestingly, TGF-β1 did not modulate EGF-induced p70 S6 kinase activity, which is important for the progression of cells from the G0 to the G1 phase of the cell cycle. Immunoprecipitation of type I and type II TGF-β receptors showed that PI 3-kinase was associated with both type I and type II TGF-β receptors. TGF-β1, however, enhanced PI 3-kinase activity associated with the type I TGF-β receptor. Although in some cell types inhibition of PI 3-kinase and treatment of cells with TGF-β1 mediate apoptosis, cell cycle analysis and DNA ladder studies show that PI 3-kinase inhibition or stimulation of hASM cells with TGF-β1 did not induce myocyte apoptosis. Although the inhibitory effects of TGF-β1 on hASM cell growth are not mediated at the level of PI 3-kinase and p70 S6 kinase, we now show that activation of the TGF-β1 receptor modulates PI 3-kinase activity stimulated by growth factors in hASM cells.

scholarly journals Oligomeric Structure of Type I and Type II Transforming Growth Factor β Receptors: Homodimers Form in the ER and Persist at the Plasma Membrane

1998 ◽  
Vol 140 (4) ◽  
pp. 767-777 ◽  
Author(s):  
Lilach Gilboa ◽  
Rebecca G. Wells ◽  
Harvey F. Lodish ◽  
Yoav I. Henis
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Live Cells ◽  
Type I ◽  
Type Ii ◽  
Oligomeric Structure ◽  
The Past ◽  
Approaches To Study ◽  
Tgf Β1

Abstract. Transforming growth factor β (TGF-β) signaling involves interactions of at least two different receptors, types I (TβRI) and II (TβRII), which form ligand-mediated heteromeric complexes. Although we have shown in the past that TβRII in the absence of ligand is a homodimer on the cell surface, TβRI has not been similarly investigated, and the site of complex formation is not known for either receptor. Several studies have indicated that homomeric interactions are involved in TGF-β signaling and regulation, emphasizing the importance of a detailed understanding of the homooligomerization of TβRI or TβRII. Here we have combined complementary approaches to study these homomeric interactions in both naturally expressing cell lines and cells cotransfected with various combinations of epitope-tagged type I or type II receptors. We used sedimentation velocity of metabolically labeled receptors on sucrose gradients to show that both TβRI and TβRII form homodimer-sized complexes in the endoplasmic reticulum, and we used coimmunoprecipitation studies to demonstrate the existence of type I homooligomers. Using a technique based on antibody-mediated immunofluorescence copatching of receptors carrying different epitope tags, we have demonstrated ligand-independent homodimers of TβRI on the surface of live cells. Soluble forms of both receptors are secreted as monomers, indicating that the ectodomains are not sufficient to mediate homodimerization, although TGF-β1 is able to promote dimerization of the type II receptor ectodomain. These findings may have important implications for the regulation of TGF-β signaling.

Heat-Etching with a Bullivant Type II Simple Freeze-Cleave Device

1970 ◽  
Vol 28 ◽  
pp. 106-107 ◽  
Author(s):  
Ronald S. Weinstein ◽  
N. Scott McNutt
Keyword(s):  
New Zealand ◽  
General Hospital ◽  
Massachusetts General Hospital ◽  
Type I ◽  
Type Ii ◽  
Collaborative Effort ◽  
Temperature And Pressure ◽  
The University

The Type I simple cold block device was described by Bullivant and Ames in 1966 and represented the product of the first successful effort to simplify the equipment required to do sophisticated freeze-cleave techniques. Bullivant, Weinstein and Someda described the Type II device which is a modification of the Type I device and was developed as a collaborative effort at the Massachusetts General Hospital and the University of Auckland, New Zealand. The modifications reduced specimen contamination and provided controlled specimen warming for heat-etching of fracture faces. We have now tested the Mass. General Hospital version of the Type II device (called the “Type II-MGH device”) on a wide variety of biological specimens and have established temperature and pressure curves for routine heat-etching with the device.

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