TY - JOUR
T1 - p38/RK is essential for stress-induced nuclear responses
T2 - JNK/SAPKs and c-Jun/ATF-2 phosphorylation are insufficient
AU - Hazzalin, Catherine A.
AU - Cano, Eva
AU - Cuenda, Ana
AU - Barratt, Michael J.
AU - Cohen, Philip
AU - Mahadevan, Louis C.
N1 - Funding Information:
We thank M. Karin for GST–c-Jun fusion plasmids, A. Nebreda for MalE–XMpk2 fusion plasmids, C. Marshall for GST–MAPKAP K-2 fusion plasmids, J. Lee for SB 203580, and N. Jones, D. Gillespie and E. Black for advice, reagents and help with ATF-2 and c-Jun phosphorylation assays. Members of the Nuclear Signalling Laboratory are gratefully acknowledged for discussions and comments on this manuscript. This work is funded by the Cancer Research Campaign (C.A.H.), European Union (E.C.), Wellcome Trust (M.J.B.), MRC (P.C.) and Royal Society (P.C.).
PY - 1996
Y1 - 1996
N2 - The ERK, JNK/SAPK and p38/RK MAP kinase subtypes (reviewed in [1]) are differentially activated in mammalian cells by various stimuli, which elicit induction of immediate-early (IE) genes, such as c-fos and c-jun (reviewed in [1-3]), as well as phosphorylation of histone H3 [4] and HMG-14 [5]. Anisomycin and UV radiation have been suggested to induce c-fos and c-jun transcription via JNK/SAPK-mediated phosphorylation of TCF (ternary complex factor), for c-fos induction [6-8], and c-jun and/or ATF-2 for c-jun induction [9-13]. We report here that anisomycin and ultraviolet radiation (UV) activate MAP kinase kinase-6 (MKK6) [14,15], p38/RK [16-18] and MAPKAP kinase-2 (MAPKAP K-2) [17-19]. By using the p38/RK inhibitor SB 203580 [20,21], we show that activation of p38/RK and/or its downstream effectors are essential for anisomycin- and UV-stimulated c-fos/c-jun induction and histone H3/HMG-14 phosphorylation, whereas JNK/SAPK activation and phosphorylation of c-jun and ATF-2 are insufficient for these responses.
AB - The ERK, JNK/SAPK and p38/RK MAP kinase subtypes (reviewed in [1]) are differentially activated in mammalian cells by various stimuli, which elicit induction of immediate-early (IE) genes, such as c-fos and c-jun (reviewed in [1-3]), as well as phosphorylation of histone H3 [4] and HMG-14 [5]. Anisomycin and UV radiation have been suggested to induce c-fos and c-jun transcription via JNK/SAPK-mediated phosphorylation of TCF (ternary complex factor), for c-fos induction [6-8], and c-jun and/or ATF-2 for c-jun induction [9-13]. We report here that anisomycin and ultraviolet radiation (UV) activate MAP kinase kinase-6 (MKK6) [14,15], p38/RK [16-18] and MAPKAP kinase-2 (MAPKAP K-2) [17-19]. By using the p38/RK inhibitor SB 203580 [20,21], we show that activation of p38/RK and/or its downstream effectors are essential for anisomycin- and UV-stimulated c-fos/c-jun induction and histone H3/HMG-14 phosphorylation, whereas JNK/SAPK activation and phosphorylation of c-jun and ATF-2 are insufficient for these responses.
UR - http://www.scopus.com/inward/record.url?scp=0030220456&partnerID=8YFLogxK
U2 - 10.1016/S0960-9822(02)00649-8
DO - 10.1016/S0960-9822(02)00649-8
M3 - Article
C2 - 8805335
AN - SCOPUS:0030220456
SN - 0960-9822
VL - 6
SP - 1028
EP - 1031
JO - Current Biology
JF - Current Biology
IS - 8
ER -