Abstract
Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate with each other and with additional pathways, creating a signaling network that is important for cell fate determination. In this review, we focus on ERK, JNK, p38 and ERK5, the major MAPKs, and their interactions with PI3K-Akt, TGFβ/Smad and Wnt/β-catenin pathways. More importantly, we describe how MAPKs regulate cell proliferation and differentiation in the rapidly renewing epithelia that lines the gastrointestinal tract and, finally, we highlight the recent findings on nutritional aspects that affect MAPK transduction cascades.
Highlights
During their life, cells are exposed to several external and internal agents and their combination determines cell fate
We focused on the role of Mitogen-activated protein kinase (MAPK) and their major partners in the signaling networks that lead to epithelial cell proliferation and differentiation, and we summarized recent findings on nutritional aspects that can influence MAPK pathway
MEKK2 and MEKK3 are activated to phosphorylate MEK5, which directly phosphorylates ERK5, and this MAPK acts on different substrates such as myocyte enhancer factor 2C (MEF2) transcription factor, that culminates in increased expression of c-Jun [24,25]
Summary
Cells are exposed to several external and internal agents and their combination determines cell fate. Mitogen-activated protein kinases (MAPKs) are important signaling molecules that influence a broad range of cellular processes such as proliferation, differentiation, migration and apoptosis. Since their discovery in the 1980s, MAPKs have been extensively studied (for a historic description, see Avruch [1]) and several reports show that this signaling pathway is highly conserved amongst eukaryotes. We focused on the role of MAPKs and their major partners in the signaling networks that lead to epithelial cell proliferation and differentiation, and we summarized recent findings on nutritional aspects that can influence MAPK pathway
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