Premium
Cytoplasmic c‐Fos induced by the YXXQ‐derived STAT3 signal requires the co‐operative MEK/ERK signal for its nuclear translocation
Author(s) -
Higashi Natsuko,
Kunimoto Hiroyuki,
Kaneko Shuhei,
Sasaki Takanori,
Ishii Masamitsu,
Kojima Hirotada,
Nakajima Koichi
Publication year - 2004
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1356-9597.2004.00715.x
Subject(s) - mapk/erk pathway , cytoplasm , biology , stat protein , microbiology and biotechnology , nucleus , signal transduction , activator (genetics) , nuclear localization sequence , c fos , stat3 , gene expression , receptor , biochemistry , gene
A STAT3 (signal transducer and activator of transcription 3)‐ and a MEK/Erk‐mediated signal can be activated by cytokines, including IL‐6 (interleukin‐6), PDGF, and EGF. Recently, STAT3 and an ERK‐signal were shown to co‐operatively activate the c‐fos gene. Activation of a truncated form of the IL‐6 receptor subunit, gp130, that had only one YXXQ motif, induced both c‐Fos and JunB in NIH3T3 cells through STAT3 without an apparent increase in the AP‐1 (activator protein‐1) activity. In contrast, concomitant stimulation of the STAT3 signal and a MEK/Erk‐signal markedly increased AP‐1 activity with enhanced c‐Fos expression. Surprisingly, the c‐Fos induced by the YXXQ‐signal alone was localized to the cytoplasm, from which it translocated into the nucleus following TPA (12‐O‐tetradecanoyl‐phorbol 13‐acetate) treatment in a MEK/Erk‐dependent manner. c‐Fos that was expressed from a constitutive promoter localized to the nucleus and did not move into the cytoplasm in response to the YXXQ‐signal. Rather, the YXXQ‐signal was required during c‐Fos production for it to be retained in the cytoplasm. Thus, the YXXQ‐signal induces c‐Fos expression through STAT3 and anchors the new c‐Fos in the cytoplasm. In addition, the YXXQ‐signal and an Erk signal co‐operatively cause c‐Fos activation in the nucleus.