Constitutive activation of the MAPK pathway mediates v-fes-induced mitogenesis in murine macrophages

Autor(en)

Elisabetta Rovida, Fabio Marra, Manuela Baccarini, Persio Dello Sbarba

Abstrakt

Fes is a nonreceptor tyrosine kinase expressed at the highest level in macrophages. We previously showed that the overexpression of c-fes in murine macrophages of the BAC-1.2F5 cell line renders these cells independent of macrophage colony-stimulating factor (MCSF) for survival and proliferation, although no direct relationship could be established between tyrosine- phosphorylated substrates of Fes- and MCSF receptor-dependent signaling and mitogenesis. In this study, we investigated whether the mitogen-activated protein kinase (MAPK) pathway is involved in the growth factor-independent growth of v-fes-overexpressing macrophages. We found a constitutively increased phosphorylation of extracellularly regulated kinase (ERK) in v-fes- overexpressing macrophages as compared with mock-infected cells. This finding was associated with activation of mitogen/extracellular signal-regulated kinase (MEK) and with constitutive localization of ERK in the nucleus. Treatment of v-fes-overexpressing cells with the MEK-specific inhibitor PD98059 markedly reduced cell growth, hyperphosphorylation, and nuclear localization of ERK, indicating that the MAPK pathway mediates the mitogenic effect of v-fes. (C) 2000 by The American Society of Hematology.

Organisation(en)

Externe Organisation(en)

Università degli Studi di Firenze

Journal

Blood

Band

95

Seiten

3959-3963

Anzahl der Seiten

5

ISSN

0006-4971

Publikationsdatum

2000

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/constitutive-activation-of-the-mapk-pathway-mediates-vfesinduced-mitogenesis-in-murine-macrophages(62b34bfb-3263-421a-8922-f32a3677b3b0).html