Stress-activated protein kinases are negatively regulated by cell density

被引:82
作者
Lallemand, D
Ham, J
Garbay, S
Bakiri, L
Traincard, F
Jeannequin, O
Pfarr, CM
Yaniv, M
机构
[1] Inst Pasteur, Dept Biotechnol, CNRS, Unite Virus Oncogenes 1644, F-75724 Paris 15, France
[2] Inst Pasteur, Dept Biotechnol, Lab Hybridolab, F-75724 Paris, France
[3] Univ London Univ Coll, Eisai London Res Labs, London WC1E 6BT, England
[4] Texas Tech Univ, Sch Med, Dept Cell Biol & Biochem, Lubbock, TX USA
关键词
c-Jun; JNK; SAPK pathway; mouse fibroblasts; protein kinase; stress activation;
D O I
10.1093/emboj/17.19.5615
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Stimulation by UV irradiation, TNF alpha, as well as PDGF or EGF activates the JNK/SAPK signalling pathway in mouse fibroblasts, This results in the phosphorylation of the N-terminal domain of c-Jun, increasing its transactivation potency. Using an antibody that specifically recognizes c-Jun phosphorylated at Ser63, we show that culture conflueucy drastically inhibited c-Jun N-terminal phosphorylation due to the inhibition of the JNK/SAPK pathway. Transfection experiments demonstrate that the inhibition occurs at the same level as, or upstream of, the small G-proteins cdc42 and Rad. In contrast, the classical MAPK pathway was insensitive to conflueucy, The inhibition of JNK/SAPK activation depended on the integrity of the actin microfilament network. These results were confirmed and extended in monolayer wounding experiments. After PDGF, EGF or UV stimulation, c-Jun was predominantly phosphorylated in cells bordering the wound, which are the cells that move to occupy the wounded area. Thus, modulation of the stress-dependent signal cascade by conflueucy will restrict c-dun N-terminal phosphorylation in response to mitogenic or chemotactic agents to cells that border a wounded area.
引用
收藏
页码:5615 / 5626
页数:12
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