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JAM‐A regulates epithelial proliferation through Akt/β‐catenin signalling
Author(s) -
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
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.16
Subject(s) - protein kinase b , microbiology and biotechnology , catenin , cell growth , transcription factor , pi3k/akt/mtor pathway , cancer research , chemistry , signal transduction , biology , wnt signaling pathway , biochemistry , gene
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 β‐catenin activation. Furthermore, IECs from transgenic JAM‐A −/− /β‐catenin/T‐cell factor reporter mice showed enhanced β‐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.