Regulation of adherens junction protein p120ctnby 10 nM CCK precedes actin breakdown in rat pancreatic acini

2000 ◽  
Vol 278 (3) ◽  
pp. G486-G491 ◽  
Author(s):  
J. Leser ◽  
M. F. Beil ◽  
O. A. Musa ◽  
G. Adler ◽  
M. P. Lutz
Keyword(s):  
Tyrosine Phosphorylation ◽  
Actin Filament ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Acinar Cells ◽  
Pancreatic Acini ◽  
Filament System ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
E Cadherin

The initial pathophysiological events that characterize CCK-hyperstimulation pancreatitis include the breakdown of the actin filament system and disruption of cadherin-catenin protein complexes. Cadherins and catenins are part of adherens junctions, which may act as anchor for the cellular actin filament system. We examined the composition and regulation of adherens junctions during CCK-induced acinar cell damage. Freshly isolated CCK-stimulated rat pancreatic acini were examined for actin filaments and functional adherens junctions by immunocytology and laser confocal scanning microscopy or by coprecipitation and immunoblotting for E-cadherin, β- and α-catenin, p120ctn, and phosphotyrosine. In addition to E-cadherin and β-catenin, acinar cells express the cadherin-regulatory protein p120ctn and the attachment protein α-catenin. Both colocalize and coimmunoprecipitate with E-cadherin in one complex, and all colocalize with the terminal actin web. Supramaximal secretory CCK concentrations (10 nM) initiated tyrosine phosphorylation of p120ctn but not of β-catenin within 2 min, preceding the breakdown of the terminal actin web by several minutes. Under these conditions, the cadherin-catenin association within the adherens junction complex remained intact. We describe for the first time supramaximal CCK-dependent tyrosine phosphorylation of the adherens junction protein p120ctnand demonstrate the presence of an intact adherens junction protein complex in acinar cells. p120ctn may participate in the actin filament breakdown during experimental conditions mimicking pancreatitis.

scholarly journals Abelson kinase regulates epithelial morphogenesis in Drosophila

2001 ◽  
Vol 155 (7) ◽  
pp. 1185-1198 ◽  
Author(s):  
Elizabeth E. Grevengoed ◽  
Joseph J. Loureiro ◽  
Traci L. Jesse ◽  
Mark Peifer
Keyword(s):  
Epithelial Cells ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Epithelial Morphogenesis ◽  
Actin Dynamics ◽  
Nonreceptor Tyrosine Kinase ◽  
Abelson Kinase ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Guidance Receptors

Activation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and α-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

scholarly journals PLEKHA7, an apical adherens junction protein, suppresses inflammatory breast cancer in the context of high E-cadherin and p120-catenin expression.

2020 ◽  
Author(s):  
Lindy J Pence ◽  
Antonis Kourtidis ◽  
Ryan W. Feathers ◽  
Mary T. Haddad ◽  
Sotiris Sotiriou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Inflammatory Breast Cancer ◽  
Adherens Junction ◽  
Major Protein ◽  
Breast Cancers ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
E Cadherin

Abstract Background: Inflammatory breast cancer is a highly aggressive form of breast cancer that robustly forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. Inflammatory breast cancers express high levels of E-cadherin, the major protein of adherens junctions, which may enhance the ability of tumor cells to form such clusters and contribute to metastasis. Seemingly contradictory, E-cadherin has both tumor-suppressing and tumor-promoting roles in cancer; previous studies suggest that this depends on the balance between apical and basolateral cadherin-catenin complexes. Methods: In the present study, we use immunohistochemistry of inflammatory breast cancer patient samples and biochemical analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We use viral transduction to ectopically express PLEKHA7 in the SUM149 inflammatory breast cancer cell line. The effect of PLEKHA7 on the aggressiveness of inflammatory breast cancer in 2D, 3D and in-vivo were examined. Results: We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in a strong majority of patient samples and very low expression in cell line models. We found that re-expressing PLEKHA7 is sufficient to suppress proliferation, anchorage independent growth, spheroid viability, and tumor growth in-vivo. We also observed a negative-selection pressure within the xenograft tumors to lose PLEKHA7 function or expression.Conclusions: The data indicate that PLEKHA7 is frequently deregulated and acts as a suppressor of inflammatory breast cancer. They also suggest that the resulting imbalance between apical and basolateral cadherin-catenin complexes contributes to growth, survival and emboli-forming capacities of inflammatory breast cancer.

scholarly journals PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1275
Author(s):  
Lindy J. Pence ◽  
Antonis Kourtidis ◽  
Ryan W. Feathers ◽  
Mary T. Haddad ◽  
Sotiris Sotiriou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Inflammatory Breast Cancer ◽  
Driving Forces ◽  
Adherens Junction ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Tumor Emboli ◽  
E Cadherin

Inflammatory breast cancer is a highly aggressive form of breast cancer that forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. These cancers express high levels of E-cadherin, the major mediator of adherens junctions, which enhances formation of tumor emboli. Previous studies suggest that E-cadherin promotes cancer when the balance between apical and basolateral cadherin complexes is disrupted. Here, we used immunohistochemistry of inflammatory breast cancer patient samples and analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We used viral transduction to re-express PLEKHA7 in inflammatory breast cancer cells and examined their aggressiveness in 2D and 3D cultures and in vivo. We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in most patient samples and very low expression in cell lines. Re-expressing PLEKHA7 suppressed proliferation, anchorage independent growth, spheroid viability, and tumor growth in vivo. The data indicate that PLEKHA7 is frequently deregulated and acts to suppress inflammatory breast cancer. The data also promote the need for future inquiry into the imbalance between apical and basolateral cadherin complexes as driving forces in inflammatory breast cancer.

scholarly journals An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling.

1996 ◽  
Vol 134 (5) ◽  
pp. 1283-1300 ◽  
Author(s):  
S Orsulic ◽  
M Peifer
Keyword(s):  
Structure Function ◽  
Cellular Localization ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Beta Catenin ◽  
Function Study ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Wingless Signaling

Armadillo, the Drosophila homologue of vertebrate beta-catenin, plays a pivotal role both in Wingless signaling and in assembly of adherens junctions. We performed the first in vivo structure-function study of an adherens junction protein, by generating and examining a series of Armadillo mutants in the context of the entire animal. We tested each mutant by assaying its biological function, its ability to bind proteins that normally associate with Armadillo in adherens junctions, its cellular localization, and its pattern of phosphorylation. We mapped the binding sites for DE-cadherin and alpha-catenin. Although these bind to Armadillo independently of each other, binding of each is required for the function of adherens junctions. We identified two separate regions of Armadillo critical for Wingless signaling. We demonstrated that endogenous Armadillo accumulates in the nucleus and provide evidence that it may act there in transducing Wingless signal. We found that the Arm repeats, which make up the central two-thirds of Armadillo, differ among themselves in their functional importance in different processes. Finally, we demonstrated that Armadillo's roles in adherens junctions and Wingless signaling are independent. We discuss the potential biochemical role of Armadillo in each process.

The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction

1993 ◽  
Vol 105 (4) ◽  
pp. 993-1000 ◽  
Author(s):  
M. Peifer
Keyword(s):  
Sequence Similarity ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Beta Catenin ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Drosophila Homolog ◽  
Segment Polarity ◽  
Associated Proteins ◽  
Segment Polarity Gene

Sequence similarity between the Drosophila segment polarity protein Armadillo and the vertebrate adherens junction protein beta-catenin raised the possibility that adherens junctions function in transduction of intercellular signals like that mediated by Wingless/Wnt-1. To substantiate the sequence similarity, properties of Armadillo were evaluated for consistency with a junctional role. Armadillo is part of a membrane-associated complex. This complex includes Armadillo, a glycoprotein similar in size to vertebrate cadherins, and the Drosophila homolog of alpha-catenin. Armadillo co-localizes with junctions that resemble vertebrate adherens junctions in morphology and position. These results suggest that Drosophila and vertebrate adherens junctions are structurally similar, validating use of Armadillo and its associated proteins as a model for vertebrate adherens junctions.

scholarly journals E-cadherin Surface Levels in Epithelial Growth Factor-stimulated Cells Depend on Adherens Junction Protein Shrew-1

2009 ◽  
Vol 20 (15) ◽  
pp. 3598-3607 ◽  
Author(s):  
Julia Christina Gross ◽  
Alexander Schreiner ◽  
Knut Engels ◽  
Anna Starzinski-Powitz
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Adherens Junction ◽  
Loss Of Function ◽  
Cell Dynamics ◽  
Epithelial Growth Factor ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Epithelial Growth ◽  
E Cadherin

Gain- and loss-of-function studies indicate that the adherens junction protein shrew-1 acts as a novel modulator of E-cadherin internalization induced by epithelial growth factor (EGF) or E-cadherin function-blocking antibody during epithelial cell dynamics. Knocking down shrew-1 in MCF-7 carcinoma cells preserves E-cadherin surface levels upon EGF stimulation. Overexpression of shrew-1 leads to preformation of an E-cadherin/EGF receptor (EGFR) HER2/src-kinase/shrew-1 signaling complex and accelerated E-cadherin internalization. Shrew-1 is not sufficient to stimulate E-cadherin internalization, but facilitates the actions of EGFR and thus may promote malignant progression in breast cancer cells with constitutive EGFR stimulation by reducing surface E-cadherin expression.

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