Functional Integration of the Conserved Domains of Shoc2 Scaffold.
Functional Integration of the Conserved Domains of Shoc2 Scaffold.
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DOI：
10.1371/journal.pone.0066067
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Galperin E
中科院分区：
文献类型：
--
作者：
Jeoung M;Abdelmoti L;Jang ER;Vander Kooi CW;Galperin E
Shoc2是细胞外信号调节蛋白激酶1和2 （ERK1/2）信号的正调节因子。Shoc2也被认为与RAS和Raf-1相互作用，以加速ERK1/2的活性。为了了解表皮生长因子受体（EGFR）调控ERK1/2激活的机制，我们剖析了Shoc2结构域在与其信号伙伴结合中的作用及其在调节ERK1/2活性中的作用。Shoc2由两个主要结构域组成：21亮氨酸富重复序列（lrr）核心和n端非lrr结构域。我们证明了n端结构域介导了Shoc2与M-Ras和Raf-1的结合，而Shoc2的c端部分包含一个晚期内体靶向基序。我们发现M-Ras与Shoc2的结合独立于其GTPase活性。虽然过表达Shoc2不会改变ERK1/2活性的动力学，但在缺乏Shoc2的细胞中，n端和LRR-core结构域都能够恢复ERK1/2活性，这表明这些Shoc2结构域参与调节ERK1/2活性。
Shoc2 is a positive regulator of signaling to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Shoc2 is also proposed to interact with RAS and Raf-1 in order to accelerate ERK1/2 activity. To understand the mechanisms by which Shoc2 regulates ERK1/2 activation by the epidermal growth factor receptor (EGFR), we dissected the role of Shoc2 structural domains in binding to its signaling partners and its role in regulating ERK1/2 activity. Shoc2 is comprised of two main domains: the 21 leucine rich repeats (LRRs) core and the N-terminal non-LRR domain. We demonstrated that the N-terminal domain mediates Shoc2 binding to both M-Ras and Raf-1, while the C-terminal part of Shoc2 contains a late endosomal targeting motif. We found that M-Ras binding to Shoc2 is independent of its GTPase activity. While overexpression of Shoc2 did not change kinetics of ERK1/2 activity, both the N-terminal and the LRR-core domain were able to rescue ERK1/2 activity in cells depleted of Shoc2, suggesting that these Shoc2 domains are involved in modulating ERK1/2 activity.
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影响因子：
30.8
作者：
Cordeddu, Viviana;Di Schiavi, Elia;Pennacchio, Len A.;Ma'ayan, Avi;Sarkozy, Anna;Fodale, Valentina;Cecchetti, Serena;Cardinale, Alessio;Martin, Joel;Schackwitz, Wendy;Lipzen, Anna;Zampino, Giuseppe;Mazzanti, Laura;Digilio, Maria C.;Martinelli, Simone;Flex, Elisabetta;Lepri, Francesca;Bartholdi, Deborah;Kutsche, Kerstin;Ferrero, Giovanni B.;Anichini, Cecilia;Selicorni, Angelo;Rossi, Cesare;Tenconi, Romano;Zenker, Martin;Merlo, Daniela;Dallapiccola, Bruno;Iyengar, Ravi;Bazzicalupo, Paolo;Gelb, Bruce D.;Tartaglia, Marco
通讯作者：
Tartaglia, Marco
影响因子：
3
作者：
Kajava, AV
通讯作者：
Kajava, AV
影响因子：
4.8
作者：
Kim, Ho Min;Oh, Se Cheol;Lee, Jie-Oh
通讯作者：
Lee, Jie-Oh
影响因子：
4.8
作者：
Brown MD;Sacks DB
通讯作者：
Sacks DB
DOI：
10.1111/j.1600-0854.2008.00788.x
发表时间：
2008-09
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Galperin E;Sorkin A
通讯作者：
Sorkin A