The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1.
The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1.
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DLC-1和CTEN的SH2结构域的磷酸酪氨酸独立的相互作用调节局灶性粘附定位和DLC-1的生长抑制活性。
DOI：
10.1083/jcb.200608015
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发表时间：
2007-01-01
影响因子：
7.8
通讯作者：
Lo, Su Hao
中科院分区：
文献类型：
--
作者：
Liao, Yi-Chun;Si, Lizhen;White, Ralph W. DeVere;Lo, Su Hao
张力蛋白家族成员cten（C末端张力蛋白样）是一种Src同源2（SH 2）和含有磷酸酪氨酸结合结构域的粘着斑分子，可能具有肿瘤抑制因子的作用。然而，这一机制还没有很好地建立。我们报告cten结合到另一个肿瘤抑制因子，在肝癌1（DLC-1）中删除，和cten的SH 2结构域负责的相互作用。出乎意料的是，DLC-1和cten SH 2结构域之间的相互作用不依赖于DLC-1的酪氨酸磷酸化。通过定点突变，我们已经确定了几个氨基酸残基cten和DLC-1是必不可少的这种相互作用。DLC-1上的突变扰乱了与cten的相互作用，并破坏了DLC-1的粘着斑定位。此外，这些DLC-1突变体已经失去了它们的肿瘤抑制活性。当这些DLC-1突变体与粘着斑靶向序列融合时，它们的肿瘤抑制活性显著恢复。这些结果提供了一种新的机制，其中DLC-1的cten介导的粘着斑定位的SH 2结构域在其肿瘤抑制活性中起重要作用。
The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain–containing focal adhesion molecule that may function as a tumor suppressor. However, the mechanism has not been well established. We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. By site-directed mutagenesis, we have identified several amino acid residues on cten and DLC-1 that are essential for this interaction. Mutations on DLC-1 perturb the interaction with cten and disrupt the focal adhesion localization of DLC-1. Furthermore, these DLC-1 mutants have lost their tumor suppression activities. When these DLC-1 mutants were fused to a focal adhesion targeting sequence, their tumor suppression activities were significantly restored. These results provide a novel mechanism whereby the SH2 domain of cten-mediated focal adhesion localization of DLC-1 plays an essential role in its tumor suppression activity.
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DOI：
10.1007/s00432-003-0440-z
发表时间：
2003-06-01
影响因子：
3.6
作者：
Plaumann, M;Seitz, S;Scherneck, S
通讯作者：
Scherneck, S
影响因子：
16
作者：
Poy, F;Yaffe, MB;Eck, MJ
通讯作者：
Eck, MJ
DOI：
10.1083/jcb.125.5.1067
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lo SH;Janmey PA;Hartwig JH;Chen LB
通讯作者：
Chen LB
影响因子：
4.1
作者：
Chen, HY;Lo, SH
通讯作者：
Lo, SH
影响因子：
56.9
作者：
DAVIS, S;LU, ML;CHEN, LB
通讯作者：
CHEN, LB