Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1.
Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1.
复制标题
肌细胞增强因子 2 (MEF2) 与丝裂原激活蛋白激酶 ERK5/BMK1 的相互作用。
作者：
Chih;O. Ornatsky;J. C. McDermott;T. Cruz;C. Prody
肌细胞增强因子2 （MEF2）参与了肌肉特异性基因表达和分化的复杂分层调节。虽然MyoD家族成员能够启动骨骼肌分化程序，但MEF2是否足以指导骨骼肌分化仍存在争议。此外，MEF2如何激活其靶基因尚不完全清楚。有人认为，MEF2与其他因子的相互作用改变了其转录活性。因此，鉴定MEF2相互作用因子可能对了解MEF2激活其靶基因的机制具有重要意义。在本研究中，在酵母双杂交筛选中发现有丝裂原活化蛋白激酶（MAP激酶）ERK5/BMK1与MEF2相互作用。通过谷胱甘肽S -转移酶拉下实验和免疫共沉淀研究证实了这种相互作用，表明内源性ERK5和MEF2在体内相互作用。MEF2的相互作用结构域被定位到包含高度保守的MADS和MEF2结构域的n端。在功能上，ERK5/BMK1能够在体外磷酸化MEF2。此外，当与ERK5/BMK1共转染时，MEF2的转激活能力增强。这些结果表明MEF2的功能可以通过ERK5/BMK1调控。
Myocyte enhancer factor 2 (MEF2) has been implicated in the complex hierarchical regulation of muscle-specific gene expression and differentiation. While the MyoD family members are able to initiate the skeletal muscle differentiation program, whether MEF2 is sufficient in directing skeletal muscle differentiation is still controversial. Furthermore, how MEF2 transactivates its target genes is not fully understood. It has been suggested that the interactions of MEF2 with other factors modify its transcriptional activity. Therefore, the identification of MEF2-interacting factors may be important in understanding the mechanism by which MEF2 activates its target genes. In this study, a mitogen-activated protein kinase (MAP kinase), ERK5/BMK1 was found to interact with MEF2 in a yeast two hybrid screen. The interaction was confirmed by a glutathione S -transferase-pull down assay and a co-immunoprecipitation study indicating that endogenous ERK5 and MEF2 interact with each other in vivo . The interacting domain of MEF2 was mapped to the N-terminus which contains the highly conserved MADS and MEF2 domains. Functionally, ERK5/BMK1 was able to phosphorylate MEF2 in vitro . Furthermore, when cotransfected with ERK5/BMK1, the transactivation capacity of MEF2 was enhanced. These results suggest that the functions of MEF2 could be regulated through ERK5/BMK1.
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影响因子：
56.9
作者：
Lin, Q;Schwarz, J;Olson, EN
通讯作者：
Olson, EN
影响因子：
10.5
作者：
DURFEE, T;BECHERER, K;ELLEDGE, SJ
通讯作者：
ELLEDGE, SJ
DOI：
10.1006/bbrc.1995.2189
发表时间：
1995-08-15
影响因子：
3.1
作者：
LEE, JD;ULEVITCH, RJ;HAN, JH
通讯作者：
HAN, JH
DOI：
10.1073/pnas.91.12.5662
发表时间：
1994-06-07
影响因子：
11.1
作者：
LILLY, B;GALEWSKY, S;OLSON, EN
通讯作者：
OLSON, EN
影响因子：
5.3
作者：
GOSSETT, LA;KELVIN, DJ;OLSON, EN
通讯作者：
OLSON, EN