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The regulation of alternative splicing by extracellular signals represents a key event in the control of gene expression. There is increasing evidence showing that many extracellular cues regulate alternative splicing. Nevertheless, the broad picture regarding the role of different signaling pathways and their interaction remains incomplete. Using the fibronectin gene as a model, we show that a laminin-rich basement membrane regulates the alternative splicing of two out of three regions of the transcript (extra domain I and type III connecting segment) in mammary epithelial cells, through a non-stress c-Jun N-terminal kinase (JNK) signaling pathway. We propose that dephosphorylation of the extracellular signal-regulated kinase is involved in this regulatory process. Furthermore, the laminin-rich basement membrane blocks the effect of a mammary mesenchymal cell-conditioned medium, which stimulates the inclusion of extra domain I and type III connecting segment through a phosphatidylinositol 3-kinase-dependent cascade, indicating that JNK signaling can inhibit the phosphatidylinositol 3-kinase-mediated splicing regulation. These results implicate JNK in the regulation of alternative splicing and provide new evi-dence on how extracellular stimuli are converted into changes in splicing patterns, strengthening the view that the control of alternative splicing is as complex and relevant as transcriptional control, together accounting for the spatiotemporal requirements of gene expression. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.


Documento: Artículo
Título:Cross-talk between signaling pathways regulates alternative splicing: A novel role for JNK
Autor:Pelisch, F.; Blaustein, M.; Kornblihtt, A.R.; Srebrow, A.
Filiación:Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Biological membranes; Cells; Computer simulation; Enzyme inhibition; Enzymes; Genes; Mathematical models; Stresses; Fibronectin genes; Gene expression; Laminin; Splicing; Biochemistry; fibronectin; laminin; mitogen activated protein kinase; phosphatidylinositol 3 kinase; stress activated protein kinase; alternative RNA splicing; article; basement membrane; breast epithelium; controlled study; culture medium; dephosphorylation; epithelium cell; gene expression; human; human cell; mesenchyme cell; model; priority journal; protein function; signal transduction; 1-Phosphatidylinositol 3-Kinase; Alternative Splicing; Basement Membrane; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Line, Tumor; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Humans; JNK Mitogen-Activated Protein Kinases; Laminin; Mesoderm; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction; Transfection
Página de inicio:25461
Página de fin:25469
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
CAS:fibronectin, 86088-83-7; laminin, 2408-79-9; mitogen activated protein kinase, 142243-02-5; phosphatidylinositol 3 kinase, 115926-52-8; stress activated protein kinase, 155215-87-5; 1-Phosphatidylinositol 3-Kinase, EC; Extracellular Signal-Regulated MAP Kinases, EC; JNK Mitogen-Activated Protein Kinases, EC; Laminin; Protein-Serine-Threonine Kinases, EC; Proto-Oncogene Proteins c-akt, EC; Proto-Oncogene Proteins


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---------- APA ----------
Pelisch, F., Blaustein, M., Kornblihtt, A.R. & Srebrow, A. (2005) . Cross-talk between signaling pathways regulates alternative splicing: A novel role for JNK. Journal of Biological Chemistry, 280(27), 25461-25469.
---------- CHICAGO ----------
Pelisch, F., Blaustein, M., Kornblihtt, A.R., Srebrow, A. "Cross-talk between signaling pathways regulates alternative splicing: A novel role for JNK" . Journal of Biological Chemistry 280, no. 27 (2005) : 25461-25469.
---------- MLA ----------
Pelisch, F., Blaustein, M., Kornblihtt, A.R., Srebrow, A. "Cross-talk between signaling pathways regulates alternative splicing: A novel role for JNK" . Journal of Biological Chemistry, vol. 280, no. 27, 2005, pp. 25461-25469.
---------- VANCOUVER ----------
Pelisch, F., Blaustein, M., Kornblihtt, A.R., Srebrow, A. Cross-talk between signaling pathways regulates alternative splicing: A novel role for JNK. J. Biol. Chem. 2005;280(27):25461-25469.