Regulation of c‐Fos and Fra‐1 by the MEK5‐ERK5 pathway
2003; Wiley; Volume: 8; Issue: 3 Linguagem: Inglês
10.1046/j.1365-2443.2003.00631.x
ISSN1365-2443
AutoresKazuya Terasawa, Kenji Okazaki, Eisuke Nishida,
Tópico(s)Cellular Mechanics and Interactions
ResumoAbstract Background: ERK5 is the newest subfamily member of the mitogen‐activated protein kinase (MAPK) family, and is activated by various extracellular signals including growth factors. MEK5 is a specific activator of ERK5. c‐Fos and Fra‐1, well‐known immediate early gene products, are members of the AP‐1 family. We previously reported that activation of the MEK5‐ERK5 pathway is able to induce expression of c‐Fos. Results: We have found that activation of the MEK5‐ERK5 pathway causes the phosphorylation and stabilization of c‐Fos and Fra‐1. Phosphorylation of c‐Fos appears to be mediated by ERK5 and a kinase(s) lying downstream of ERK5, and the MEK5‐ERK5 pathway‐dependent phosphorylation sites on c‐Fos are different from the ERK1/2 pathway‐dependent ones. Interestingly, activation of the MEK5‐ERK5 pathway, but not that of the ERK1/2 pathway, is found to markedly increase the transactivation activity of c‐Fos. Furthermore, our results show that the C‐terminal half of ERK5 is necessary for the maximal activation of the transactivation activity of c‐Fos and Fra‐1. Conclusion: These results reveal a role of the MEK5‐ERK5 pathway in modulating the function of the Fos family proteins which is different from the role of the ERK1/2 pathway.
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