scholarly journals A Novel Transforming Growth Factor-β Receptor-interacting Protein That Is Also a Light Chain of the Motor Protein Dynein

2002 ◽  
Vol 13 (12) ◽  
pp. 4484-4496 ◽  
Author(s):  
Qian Tang ◽  
Cory M. Staub ◽  
Guofeng Gao ◽  
Qunyan Jin ◽  
Zhengke Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Light Chain ◽  
Transforming Growth Factor ◽  
Motor Protein ◽  
Transforming Growth Factor Β ◽  
Cytoplasmic Dynein ◽  
Epithelial Cell Line ◽  
Tgfβ Receptors ◽  
Tgfβ Receptor ◽  
Intermediate Chain

The phosphorylated, activated cytoplasmic domains of the transforming growth factor-β (TGFβ) receptors were used as probes to screen an expression library that was prepared from a highly TGFβ-responsive intestinal epithelial cell line. One of the TGFβ receptor-interacting proteins isolated was identified to be the mammalian homologue of the LC7 family (mLC7) of dynein light chains (DLCs). This 11-kDa cytoplasmic protein interacts with the TGFβ receptor complex intracellularly and is phosphorylated on serine residues after ligand-receptor engagement. Forced expression of mLC7-1 induces specific TGFβ responses, including an activation of Jun N-terminal kinase (JNK), a phosphorylation of c-Jun, and an inhibition of cell growth. Furthermore, TGFβ induces the recruitment of mLC7-1 to the intermediate chain of dynein. A kinase-deficient form of TGFβ RII prevents both mLC7-1 phosphorylation and interaction with the dynein intermediate chain (DIC). This is the first demonstration of a link between cytoplasmic dynein and a natural growth inhibitory cytokine. Furthermore, our results suggest that TGFβ pathway components may use a motor protein light chain as a receptor for the recruitment and transport of specific cargo along microtublules.

scholarly journals Distinct Endocytic Responses of Heteromeric and Homomeric Transforming Growth Factor β Receptors

1997 ◽  
Vol 8 (11) ◽  
pp. 2133-2143 ◽  
Author(s):  
Robert A. Anders ◽  
Sandra L. Arline ◽  
Jules J.E. Doré ◽  
Edward B. Leof
Keyword(s):  
Growth Factor ◽  
Ligand Binding ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Surface Receptor ◽  
Type I ◽  
Type Ii ◽  
Down Regulation ◽  
Tgfβ Receptors ◽  
Tgfβ Receptor

Transforming growth factor β (TGFβ) family ligands initiate a cascade of events capable of modulating cellular growth and differentiation. The receptors responsible for transducing these cellular signals are referred to as the type I and type II TGFβ receptors. Ligand binding to the type II receptor results in the transphosphorylation and activation of the type I receptor. This heteromeric complex then propagates the signal(s) to downstream effectors. There is presently little data concerning the fate of TGFβ receptors after ligand binding, with conflicting reports indicating no change or decreasing cell surface receptor numbers. To address the fate of ligand-activated receptors, we have used our previously characterized chimeric receptors consisting of the ligand binding domain from the granulocyte/macrophage colony-stimulating factor α or β receptor fused to the transmembrane and cytoplasmic domain of the type I or type II TGFβ receptor. This system not only provides the necessary sensitivity and specificity to address these types of questions but also permits the differentiation of endocytic responses to either homomeric or heteromeric intracellular TGFβ receptor oligomerization. Data are presented that show, within minutes of ligand binding, chimeric TGFβ receptors are internalized. However, although all the chimeric receptor combinations show similar internalization rates, receptor down-regulation occurs only after activation of heteromeric TGFβ receptors. These results indicate that effective receptor down-regulation requires cross-talk between the type I and type II TGFβ receptors and that TGFβ receptor heteromers and homomers show distinct trafficking behavior.

Transforming growth factor β in bovine milk: concentration, stability and molecular mass forms

1996 ◽  
Vol 151 (1) ◽  
pp. 77-86 ◽  
Author(s):  
M-L Rogers ◽  
C Goddard ◽  
G O Regester ◽  
F J Ballard ◽  
D A Belford
Keyword(s):  
Growth Factor ◽  
Molecular Mass ◽  
Transforming Growth Factor ◽  
Bovine Milk ◽  
Gel Filtration ◽  
Transforming Growth Factor Β ◽  
Exchange Chromatography ◽  
Epithelial Cell Line ◽  
Acid Activation ◽  
Chromatographic Procedure

Abstract Transforming growth factor β (TGF-β) is one of the predominant growth factors present in milk. The concentration, molecular mass forms and stability of TGF-β in bovine milk were investigated using a standard bioassay measuring the growth inhibition of a mink lung epithelial cell line. Most of the TGF-β bioactivity in milk was found to be in a latent form, which was also retained in the whey fraction. After acid activation, the total TGF-β concentration was 4·3 ± 0·8 ng and 3·7 ± 0·7 ng TGF-β per ml of milk and cheese whey respectively. Cation-exchange chromatography at pH 6·5 was used to concentrate latent whey-derived TGF-β, which could be activated by transient exposure to extremes of pH, urea or heat. Heparin did not significantly activate milk-derived TGF-β. Neutral gel filtration of the cationic whey fraction revealed a major peak of latent TGF-β with a molecular mass of 80 kDa and a smaller peak at 600 kDa. Transient acidification of the cationic whey fraction prior to neutral gel filtration, or gel filtration under acidic conditions, released low molecular mass TGF-β from both high molecular mass peaks. Whey-derived TGF-β was purified using a five-step chromatographic procedure. An N-terminal sequence was obtained for TGF-β2, which accounted for over 85% of the TGF-β bioactivity in whey. All TGF-β activity in whey could be neutralised by a monoclonal antibody directed against TGF-β1, -β2 and -β3. The results suggest that the majority of TGF-β in bovine milk is present in a small latent complex. Journal of Endocrinology (1996) 151, 77–86

scholarly journals Identification of Tctex2β, a Novel Dynein Light Chain Family Member That Interacts with Different Transforming Growth Factor-β Receptors

2006 ◽  
Vol 281 (48) ◽  
pp. 37069-37080 ◽  
Author(s):  
QingJun Meng ◽  
Andreas Lux ◽  
Andreas Holloschi ◽  
Jian Li ◽  
John M. X. Hughes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Family Member ◽  
Light Chain ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dynein Light Chain

scholarly journals The motor protein Myo1c regulates transforming growth factor-β–signaling and fibrosis in podocytes

2019 ◽  
Vol 96 (1) ◽  
pp. 139-158 ◽  
Author(s):  
Ehtesham Arif ◽  
Ashish K. Solanki ◽  
Pankaj Srivastava ◽  
Bushra Rahman ◽  
Brian R. Tash ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Motor Protein ◽  
Transforming Growth Factor Β

scholarly journals Gestational Changes in the Levels of Transforming Growth Factor-β1 (TGFβ1) and TGFβ Receptor Types I and II in the Human Myometrium1

1998 ◽  
Vol 83 (8) ◽  
pp. 2987-2992 ◽  
Author(s):  
Panadda Hatthachote ◽  
Joanna Morgan ◽  
William Dunlop ◽  
G. Nicholas Europe-Finner ◽  
James I. Gillespie
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Myometrium ◽  
Type I ◽  
Signaling System ◽  
Release Channel ◽  
Tgfβ Receptors ◽  
Tgfβ Receptor

abstract As term approaches, a number of key proteins [contraction-associated proteins (CAPs)] are expressed within the human myometrium that are essential for the activation of powerful coordinated contractions during labor. The nature of the signals that switch on the synthesis of CAPs in vivo is not known. The ryanodine-sensitive intracellular Ca2+ release channel (RyR2) is a CAP whose expression in vitro is activated by transforming growth factor-β (TGFβ). The present experiments were performed to determine whether TGFβ and TGFβ receptors are present in the human myometrium at term and to explore the idea that they might form part of a signaling system in vivo. TGFβ receptor types I and II, but not III, were demonstrated in myometrial smooth muscle in tissue taken from nonpregnant, pregnant nonlaboring, and spontaneous laboring women. Western blotting was used subsequently to determine the relative expression of TGFβ receptor types I and II. Using nonpregnant myometrium as a baseline control the levels of expression of receptor types I and II were significantly increased by 168 ± 19% (n = 6) and 162 ± 22% (n = 7) in pregnant nonlaboring myometrium. In spontaneous laboring myometrium the levels of TGFβ receptor type I and II expression were 93 ± 12% (n = 6) and 85 ± 11% (n = 7), respectively, compared to nonpregnant control values and were significantly lower than levels in pregnant nonlaboring tissues. The total TGFβ1 levels in the myometrial tissues were 334 ± 10, 534 ± 73, and 674 ± 106 pg/g tissue wet wt in nonpregnant, pregnant nonlaboring, and spontaneous laboring myometrium (n = 3 in each group), respectively. Thus, the TGFβ signaling system appears to be up-regulated in the myometrium before the onset of parturition. The apparent loss of receptors in the spontaneous laboring samples in the presence of elevated total levels of TGFβ may be indicative of agonist-induced receptor down-regulation. These observations support the idea that cytokines, in particular TGFβ1, may play a role in the normal processes that prepare the myometrium for parturition at term.

scholarly journals Differential Trafficking of Transforming Growth Factor-β Receptors and Ligand in Polarized Epithelial Cells

2004 ◽  
Vol 15 (6) ◽  
pp. 2853-2862 ◽  
Author(s):  
S. J. Murphy ◽  
J. J. E. Doré ◽  
M. Edens ◽  
R. J. Coffey ◽  
J. A. Barnard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Mdck Cells ◽  
Transforming Growth Factor Β ◽  
Confocal Imaging ◽  
Cell Contact ◽  
Type I ◽  
Tgfβ Receptors ◽  
Cell Cell

Epithelial cells in vivo form tight cell-cell associations that spatially separate distinct apical and basolateral domains. These domains provide discrete cellular processes essential for proper tissue and organ development. Using confocal imaging and selective plasma membrane domain activation, the type I and type II transforming growth factor-β (TGFβ) receptors were found to be localized specifically at the basolateral surfaces of polarized Madin-Darby canine kidney (MDCK) cells. Receptors concentrated predominantly at the lateral sites of cell-cell contact, adjacent to the gap junctional complex. Cytoplasmic domain truncations for each receptor resulted in the loss of specific lateral domain targeting and dispersion to both the apical and basal domains. Whereas receptors concentrate basolaterally in regions of direct cell-cell contact in nonpolarized MDCK cell monolayers, receptor staining was absent from areas of noncell contact. In contrast to the defined basolateral polarity observed for the TGFβ receptor complex, TGFβ ligand secretion was found to be from the apical surfaces. Confocal imaging of MDCK cells with an antibody to TGFβ1 confirmed a predominant apical localization, with a stark absence at the basal membrane. These findings indicate that cell adhesion regulates the localization of TGFβ receptors in polarized epithelial cultures and that the response to TGFβ is dependent upon the spatial distribution and secretion of TGFβ receptors and ligand, respectively.

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