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JAM-A regulates epithelial proliferation through Akt/beta-catenin signalling
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Whitehead Biomedical Research Building, Atlanta, Georgia, USA.
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Whitehead Biomedical Research Building, Atlanta, Georgia, USA.
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Whitehead Biomedical Research Building, Atlanta, Georgia, USA.
Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Whitehead Biomedical Research Building, Atlanta, Georgia, USA.
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2011 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 12, no 4, 314-20 p.Article in journal (Refereed) Published
Abstract [en]

Expression of the tight junction protein junctional adhesion molecule-A (JAM-A) has been linked to proliferation and tumour progression. However, a direct role for JAM-A in regulating proliferative processes has not been shown. By using complementary in vivo and in vitro approaches, we demonstrate that JAM-A restricts intestinal epithelial cell (IEC) proliferation in a dimerization-dependent manner, by inhibiting Akt-dependent beta-catenin activation. Furthermore, IECs from transgenic JAM-A(-/-)/beta-catenin/T-cell factor reporter mice showed enhanced beta-catenin-dependent transcription. Finally, inhibition of Akt reversed colonic crypt hyperproliferation in JAM-A-deficient mice. These data establish a new link between JAM-A and IEC homeostasis.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2011. Vol. 12, no 4, 314-20 p.
Keyword [en]
junctional adhesion molecule; Akt; b-catenin; cell proliferation; tight junction
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-141664DOI: 10.1038/embor.2011.16ISI: 000289073200010PubMedID: 21372850Scopus ID: 2-s2.0-79953312227ISBN: 1469-3178 (Electronic) 1469-221X (Linking) OAI: oai:DiVA.org:liu-141664DiVA: diva2:1149700
Note

Nava, Porfirio Capaldo, Christopher T Koch, Stefan Kolegraff, Keli Rankin, Carl Robert Farkas, Attila E Feasel, Mattie E Li, Linheng Addis, Caroline Parkos, Charles A Nusrat, Asma eng R01 DK079392/DK/NIDDK NIH HHS/ DK55679/DK/NIDDK NIH HHS/ R29 DK055679/DK/NIDDK NIH HHS/ T32 GM008169/GM/NIGMS NIH HHS/ DK72564/DK/NIDDK NIH HHS/ DK64399/DK/NIDDK NIH HHS/ R01 DK072564/DK/NIDDK NIH HHS/ DK53202/DK/NIDDK NIH HHS/ R24 DK064399/DK/NIDDK NIH HHS/ DK59888/DK/NIDDK NIH HHS/ DK79392/DK/NIDDK NIH HHS/ R01 DK055679/DK/NIDDK NIH HHS/ R01 DK061379/DK/NIDDK NIH HHS/ R01 DK059888/DK/NIDDK NIH HHS/ DK61379/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2011/03/05 06:00 EMBO Rep. 2011 Apr;12(4):314-20. doi: 10.1038/embor.2011.16. Epub 2011 Mar 4.

Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2017-10-24Bibliographically approved

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