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J Biol Chem 2018 Jun 01;29322:8342-8361. doi: 10.1074/jbc.RA117.000992.
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The atypical mitogen-activated protein kinase ERK3 is essential for establishment of epithelial architecture.

Takahashi C , Miyatake K , Kusakabe M , Nishida E .

Epithelia contribute to physical barriers that protect internal tissues from the external environment and also support organ structure. Accordingly, establishment and maintenance of epithelial architecture are essential for both embryonic development and adult physiology. Here, using gene knockout and knockdown techniques along with gene profiling, we show that extracellular signal-regulated kinase 3 (ERK3), a poorly characterized atypical mitogen-activated protein kinase (MAPK), regulates the epithelial architecture in vertebrates. We found that in Xenopus embryonic epidermal epithelia, ERK3 knockdown impairs adherens and tight-junction protein distribution, as well as tight-junction barrier function, resulting in epidermal breakdown. Moreover, in human epithelial breast cancer cells, inhibition of ERK3 expression induced thickened epithelia with aberrant adherens and tight junctions. Results from microarray analyses suggested that transcription factor AP-2α (TFAP2A), a transcriptional regulator important for epithelial gene expression, is involved in ERK3-dependent changes in gene expression. Of note, TFAP2A knockdown phenocopied ERK3 knockdown in both Xenopus embryos and human cells, and ERK3 was required for full activation of TFAP2A-dependent transcription. Our findings reveal that ERK3 regulates epithelial architecture, possibly together with TFAP2A.

PubMed ID: 29674317
PMC ID: PMC5986203
Article link: J Biol Chem

Species referenced: Xenopus laevis
Genes referenced: atp1b1 cdh1 egr4 hinfp klf4 klf5 krt12.1 mapk6 myc nhs odc1 pam sp1 sp2 sp3 tfap2a tfap2b tfap2c tfcp2l1 zeb1 zfx zic1 zic3 zic4
GO keywords: MAP kinase activity [+]
Antibodies: Acta1 Ab9 Cdh1 Ab1 Mapk6 Ab1 Myc Ab5 Tjp1 Ab1 V5 Ab3
Morpholinos: mapk6 MO1 mapk6 MO2 mapk6 MO3 tfap2a MO3 tfap2a MO4

Disease Ontology terms: branchiooculofacial syndrome
GEO Series: GSE110427: NCBI
GSE110428: NCBI
GSE110429: NCBI

Article Images: [+] show captions
References [+] :
Al-Mahdi, A novel role for atypical MAPK kinase ERK3 in regulating breast cancer cell morphology and migration. 2015, Pubmed