Transforming growth factor-β-mediated mast cell migration depends on mitogen-activated protein kinase activity

2001 ◽  
Vol 13 (7) ◽  
pp. 483-490 ◽  
Author(s):  
Niclas Olsson ◽  
Ester Piek ◽  
Magnus Sundström ◽  
Peter ten Dijke ◽  
Gunnar Nilsson
Keyword(s):  
Mast Cell ◽  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Protein Kinase Activity ◽  
Mitogen Activated Protein

scholarly journals Specific Activation of Mitogen-activated Protein Kinase by Transforming Growth Factor-β Receptors in Lipid Rafts Is Required for Epithelial Cell Plasticity

2009 ◽  
Vol 20 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Wei Zuo ◽  
Ye-Guang Chen
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Lipid Rafts ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Coated Pits ◽  
Mapk Activation ◽  
Mitogen Activated Protein

Transforming growth factor (TGF)-β regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-β can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-β–induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-β–induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-β–induced EMT and cell migration, whereas PI3K/Akt is necessary only for TGF-β–promoted cell migration but not for EMT. Although receptor heterocomplexes could be formed in both lipid raft and nonraft membrane compartments in response to TGF-β, receptor localization in lipid rafts, but not in clathrin-coated pits, is important for TGF-β–induced MAPK activation. Requirement of lipid rafts for MAPK activation was further confirmed by specific targeting of the intracellular domain of TGF-β type I receptor to different membrane locations. Together, our findings establish a novel link between cholesterol and EMT and cell migration, that is, cholesterol-rich lipid rafts are required for TGF-β–mediated MAPK activation, an event necessary for TGF-β–directed epithelial plasticity.

scholarly journals Isoflavones regulate secretion of leukemia inhibitory factor and transforming growth factor β and expression of glycodelin in human endometrial epithelial cells

2007 ◽  
Vol 196 (2) ◽  
pp. 425-433 ◽  
Author(s):  
Jin-Wen Xu ◽  
Naomi Yasui ◽  
Katsumi Ikeda ◽  
Wei-Jun Pan ◽  
June Watanabe ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Leukemia Inhibitory Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Ishikawa Cells ◽  
Endometrial Epithelial Cells

Isoflavones have attracted much attention due to their association with health benefits; however, comprehensive understanding of the beneficial impacts of isoflavones on uterine biology at the molecular level remains unexplored. In the present study, our data showed that isoflavones aglycones AglyMax, genistein, and equol, but not daidzein, within the range of plasma concentration, displayed bioavailability in regulating the secretion of leukemia inhibitory factor (LIF) and transforming growth factor β (TGF-β) in Ishikawa cells, which was blocked by an estrogen receptor antagonist ICI 182 780, mitogen-activated protein kinase kinase (MEK)1/2 inhibitor PD98059, and p38 mitogen-activated protein kinase inhibitor SB203580. We also found that AglyMax and genistein increased in cyclic AMP release and the expression of glycodelin protein in Ishikawa cells assayed using western blot and immunochemical staining. The MEK1/2 inhibitor PD98059 and the protein kinase A inhibitor H89, but not SB203580, attenuated this glycoprotein expression. Moreover, isoflavone aglycones AglyMax stimulated LIF, and TGF-β secretion, and glycodelin expression in separate primary endometrial epithelial cells in the follicular phase or luteal phase from healthy subject donors. Overall, our findings suggest that isoflavones may alter the uterine expression of estrogen-responsive genes.

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