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A role for MEK kinase 1 in TGF‐β/activin‐induced epithelium movement and embryonic eyelid closure
Author(s) -
Zhang Lin,
Wang Wei,
Hayashi Yasuhito,
Jester James V.,
Birk David E.,
Gao Min,
Liu ChiaYang,
Kao Winston W.Y.,
Karin Michael,
Xia Ying
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg440
Subject(s) - biology , activin receptor , embryonic stem cell , epithelium , microbiology and biotechnology , kinase , smad2 protein , transforming growth factor , closure (psychology) , eyelid , anatomy , endocrinology , transforming growth factor beta , genetics , gene , medicine , surgery , economics , market economy
MEKK1‐deficient mice show an eye open at birth phenotype caused by impairment in embryonic eyelid closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the eyelid epithelium, which displays loose cell–cell contacts and prominent F‐actin fibers in wild‐type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c ‐Jun N‐terminal phosphorylation in MEKK1‐deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF‐β and activin, but not by TGF‐α. MEKK1‐driven JNK activation is required for actin stress fiber formation, c ‐Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF‐β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF‐β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of eyelid closure by MEKK1. This study also suggests that the signaling mechanisms that control eyelid closure in mammals and dorsal closure in Drosophila are evolutionarily conserved.