Bi-directional Regulation of UV-induced Activation of p38 Kinase and c-Jun N-terminal Kinase by G Protein βγ-Subunits*
Bi-directional Regulation of UV-induced Activation of p38 Kinase and c-Jun N-terminal Kinase by G Protein βγ-Subunits*
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G 蛋白 βγ 亚基对紫外线诱导的 p38 激酶和 c-Jun N 末端激酶的双向调节*
DOI：
10.1074/jbc.m201717200
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Y. Juhnn
中科院分区：
文献类型：
--
作者：
M. Seo;Yun;C. Cho;C. Bae;In;Y. Juhnn
紫外线（UV）照射通过激活包括丝裂原活化蛋白激酶（MAPK）在内的多种UV应答酶诱导多种细胞应答。各种G蛋白偶联受体激动剂也激活MAPK，但不知道G蛋白是否也介导UV诱导的MAPK激活。因此，本研究旨在确定G蛋白βγ-亚基（Gβγ）是否介导UV诱导的p38和JNK活化。COS-1细胞中Gβγ过表达增强了UV诱导的p38激活，但降低了JNK激活。β-肾上腺素能受体激酶（βARKct）C端区域的过表达降低了紫外线诱导的p38激活，但增加了JNK激活。Gβ1γ2表达增加MKK 3/6磷酸化，同时MKK 4磷酸化减少，这与βARKct表达相反。Gβ1γ2或βARKct的表达导致CHOP和c-Jun转录活性的相应变化。用p38抑制剂SB 203580处理或表达激酶失活的p38增加UV诱导的JNK激活。组成型活性MKK 6的表达降低了UV诱导的JNK活化。综上所述，虽然发现内源性Gβγ介导了约一半的UV诱导的p38激活，但发现外源性Gβγ介导了UV诱导的p38和JNK激活的双向调节，并且这种双向调节是通过在COS-1细胞中通过Gβγ激活的p38抑制JNK激活的结果。
Ultraviolet (UV) irradiation induces various cellular responses by activating many UV-responsive enzymes including mitogen-activated protein kinases (MAPKs). Various G protein-coupled receptor agonists also activate MAPKs, but it is not known whether or not G proteins also mediate the UV-induced activation of MAPKs. Therefore, this study was undertaken to determine whether the G protein βγ-subunit (Gβγ) mediates the UV-induced activation of p38 and JNK. Gβγ overexpression in COS-1 cells amplified the UV-induced activation of p38 but reduced JNK activation. The overexpression of the C-terminal region of β-adrenergic receptor kinase (βARKct) decreased the UV-induced activation of p38 but increased JNK activation. Gβ1γ2 expression increased MKK3/6 phosphorylation with a concomitant decrease in MKK4 phosphorylation, which contrasts with βARKct expression. Gβ1γ2 or βARKct expression resulted in corresponding changes in the transcriptional activity of CHOP and c-Jun. Treatment with a p38 inhibitor, SB203580, or the expression of a kinase-inactive p38 increased the UV-induced JNK activation. Expression of the constitutively active MKK6 decreased the UV-induced JNK activation. In summary, although the endogenous Gβγ was found to mediate about half of the UV–induced activation of p38, it was found that exogenous Gβγ mediates the bi-directional regulation of UV-induced p38 and JNK activation, and that this bi-directional regulation results from the inhibition of JNK activation by the p38 activated via Gβγ in the COS-1 cells.
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DOI：
10.1016/s0021-9258(17)37587-7
发表时间：
1994-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
W. Koch;B. Hawes;James Inglese;L. Luttrell;R. Lefkowitz
通讯作者：
W. Koch;B. Hawes;James Inglese;L. Luttrell;R. Lefkowitz
影响因子：
56.9
作者：
DEVARY, Y;ROSETTE, C;KARIN, M
通讯作者：
KARIN, M
DOI：
10.1073/pnas.91.26.12706
发表时间：
1994-12-20
影响因子：
11.1
作者：
KOCH, WJ;HAWES, BE;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ
影响因子：
4.8
作者：
Chen, YR;Wang, XP;Tan, TH
通讯作者：
Tan, TH