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Involvement of JAK2 upstream of the PI 3-kinase in cell-cell adhesion regulation by gastrin.

Authors: Ferrand, A  Kowalski-Chauvel, A  Bertrand, C  Pradayrol, L  Fourmy, D  Dufresne, M  Seva, C 
Citation: Ferrand A, etal., Exp Cell Res. 2004 Dec 10;301(2):128-38.
Pubmed: (View Article at PubMed) PMID:15530849
DOI: Full-text: DOI:10.1016/j.yexcr.2004.07.037

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway has been implicated in cell transformation and proliferation. Besides aberrant cell proliferation, loss of cell-cell adhesion during epithelial-mesenchymal transition (EMT) is an important event which occurs during development of epithelial cancers. However, the role of JAK-dependent pathways in this process is not known. We analyzed the involvement of these pathways in the regulation of E-cadherin-dependent cell-cell adhesion by gastrin, a mitogenic factor for gastrointestinal (GI) tract. We identified JAK2/STAT3 as a new pathway in gastrin signaling. We demonstrated that JAK2 functions as an upstream mediator of the phosphatidylinositol 3 (PI 3)-kinase activity in gastrin signaling. Indeed, we observed a coprecipitation of both kinases and an inhibition of gastrin-induced PI 3-kinase activation when JAK2 activity is blocked. We also demonstrated that loss of cell-cell adhesion and the increase in cell motility induced by gastrin required the activation of JAK2 and the PI 3-kinase. Indeed, the modifications in localization of adherens junctions proteins and the migration, observed in gastrin-stimulated cells, were reversed by inhibition of both kinases. These results described the involvement of JAK2 in the modulation of cell-cell adhesion in epithelial cells. They support a possible role of JAK2 in the epithelial-mesenchymal transition which occurs during malignant development.


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CRRD Object Information
CRRD ID: 1641930
Created: 2007-08-23
Species: All species
Last Modified: 2007-08-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.