Premium
Extracellular regulated kinase5 is expressed in fetal mouse submandibular glands and is phosphorylated in response to epidermal growth factor and other ligands of the E rb B family of receptors
Author(s) -
Koyama Noriko,
Hayashi Toru,
Mizukoshi Kenji,
Matsumoto Tsuguteru,
Gresik Edward W.,
Kashimata Masanori
Publication year - 2012
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12008
Subject(s) - mapk/erk pathway , epidermal growth factor , biology , kinase , microbiology and biotechnology , phosphorylation , extracellular , signal transduction , mitogen activated protein kinase , receptor , biochemistry
Growth factors and their receptors regulate development of many organs through activation of multiple intracellular signaling cascades including a mitogen‐activated protein kinase ( MAPK ). Extracellular regulated kinases ( ERK )1/2, classic MAPK family members, are expressed in fetal mouse submandibular glands ( SMG ), and stimulate branching morphogenesis. ERK 5, also called big mitogen‐activated protein kinase 1, was recently found as a new member of MAPK super family, and its biological roles are still largely unknown. In this study, we investigated the expression and function of ERK 5 in developing fetal mouse SMG s. Western blotting analysis showed that the expression pattern of ERK 5 was different from the pattern of ERK 1/2 in developing fetal SMG s. Both ERK 1/2 and ERK 5 were phosphorylated after exposure to ligands of the ErbB family of receptor tyrosine kinases ( RTK s). Phosphorylation of ERK 1/2 was strongly induced by epidermal growth factor ( EGF ) in SMG rudiments at embryonic day 14 ( E 14), E 16 and E 18. However, ERK 5 phosphorylation induced by EGF was clearly observed at E 14 and E 16, but not at E 18. Branching morphogenesis of cultured E 13 SMG rudiments was strongly suppressed by administration of U 0126, an inhibitor for ERK 1/2 activation, whereas the phosphorylation of ERK 5 was not inhibited by U 0126. BIX 02188, a specific inhibitor for ERK 5 activation, also inhibited branching morphogenesis in cultured SMG rudiments. These results show that EGF ‐responsive ERK 5 is expressed in developing fetal mouse SMG , and suggest that both ERK 1/2 and ERK 5 signaling cascades might play an important role in the regulation of branching morphogenesis.