The cytohesin coiled-coil domain interacts with threonine 276 to control membrane association.
The cytohesin coiled-coil domain interacts with threonine 276 to control membrane association.
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DOI：
10.1371/journal.pone.0082084
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Santy LC
中科院分区：
文献类型：
--
作者：
Hiester KG;Santy LC
细胞迁移受许多小GTP酶调节，包括Arf家族成员。细胞粘连素是Arf激活蛋白的一个家族，在迁移和细胞形状改变过程中广泛参与Arf的调节。Arf及其活化蛋白的膜缔合是Arf活化的先决条件。因此，调节细胞粘连蛋白膜缔合的程度是控制细胞运动起始的机制。我们发现了一种新的分子内相互作用，控制与细胞膜的关联。卷曲螺旋结构域的存在减少了细胞粘连素2与膜的结合。我们证明，该结构域与蛋白质的更多C-末端区域相互作用。这种相互作用是独立的另一个先前确定的自抑制构象。细胞粘连素2 PH结构域中的苏氨酸残基（T276）是Akt磷酸化的靶标。将这种苏氨酸突变为天冬氨酸，以模拟磷酸化，破坏卷曲螺旋结构域与c-末端区域的结合，并促进细胞粘连素2的膜结合。在细胞粘连素中存在第二种自身抑制相互作用，表明这些蛋白质可以作为信号整合剂，仅在接收多个促迁移信号后刺激迁移。
Cell migration is regulated by a number of small GTPases, including members of the Arf family. Cytohesins, a family of Arf-activating proteins, have been extensively implicated in the regulation of Arfs during migration and cell shape change. Membrane association of both the Arf and its activating protein is a prerequisite for Arf activation. Therefore regulating the extent of cytohesin membrane association is a mechanism for controlling the initiation of cell movement. We have discovered a novel intramolecular interaction that controls the association of cytohesins with membranes. The presence of the coiled-coil domain reduces the association of cytohesin 2 with membranes. We demonstrate that this domain interacts with more C-terminal regions of the protein. This interaction is independent of another previously identified autoinhibitory conformation. A threonine residue (T276) in the cytohesin 2 PH domain is a target for phosphorylation by Akt. Mutation of this threonine to aspartic acid, to mimic phosphorylation, disrupts the binding of the coiled-coil domain to c-terminal regions and promotes membrane association of cytohesin 2. The presence of a second autoinhibitory interaction in the cytohesins suggests that these proteins can act a signal integrators that stimulate migration only after receive multiple pro-migratory signals.
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影响因子：
3.3
作者：
Frank, SR;Hatfield, JC;Casanova, JE
通讯作者：
Casanova, JE
影响因子：
2.9
作者：
Antonny, B;BeraudDufour, S;Chabre, M
通讯作者：
Chabre, M
影响因子：
64.8
作者：
Renault, L;Guibert, B;Cherfils, J
通讯作者：
Cherfils, J
影响因子：
3.3
作者：
Cohen, Lee Ann;Honda, Akira;Donaldson, Julie G.
通讯作者：
Donaldson, Julie G.
DOI：
10.1083/jcb.200104019
发表时间：
2001-08-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Santy LC;Casanova JE
通讯作者：
Casanova JE