The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).
The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).
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DOI：
10.1016/j.cellsig.2011.06.017
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发表时间：
2011-12
影响因子：
4.8
通讯作者：
Gomez-Cambronero J
中科院分区：
文献类型：
--
作者：
Gomez-Cambronero J
PLD催化膜磷脂磷脂酰胆碱转化为胆碱和磷脂酸（PA）。PLD在细胞中的任务是双重的：磷脂转换与维持细胞/细胞膜的结构完整性和通过PA及其代谢物的细胞信号传导。确切地说，通过其反应产物PA， PLD参与了多种生理细胞功能，如细胞内蛋白质运输、细胞骨架动力学、白细胞趋化性和细胞增殖。催化结构域（HKD）和调控结构域（PH和PX）在PLD1异构体中得到了详细的研究，但PLD2的传统研究较少，对其调控的了解也较少。我们实验室一直致力于哺乳动物细胞中PLD2调控的研究。在过去的几年里，我们报道了关于PLD的催化作用，PA是一种化学引诱剂，通过核糖体S6激酶（S6K）结合并在细胞内发出信号。关于PLD2的调控结构域，我们报道了PLD2通过PX结构域的Y169与Grb2相互作用，并进一步与Sos结合，导致新生DNA合成增加，并通过邻近残基Y179与Grb2相互作用，导致细胞卷曲、趋化和白细胞吞噬的调节。我们还综述了表皮生长因子受体（EGF-R）、Janus Kinase 3 （JAK3）和Src对酪氨酸磷酸化的复杂调控以及磷酸酶的作用。最近，有证据支持PLD2在PH结构域的新水平调控，通过发现CRIB结构域和Rac2-PLD2相互作用，导致其酶活性的双重（积极和消极）影响。最后，我们回顾了PLD2作为GEF的惊人发现。存在于细胞膜中的磷脂酶，如PLD，直接作用于Rac，允许细胞在没有中间信号分子的情况下快速反应。这只提供了PLD2调控的最新水平，该领域有望在未来几年内取得更新和令人兴奋的进展。
PLD catalyzes the conversion of the membrane phospholipid phosphatidylcholine to choline and phosphatidic acid (PA). PLD's mission in the cell is two-fold: phospholipid turnover with maintenance of the structural integrity of cellular/intracellular membranes and cell signaling through PA and its metabolites. Precisely, through its product of the reaction, PA, PLD has been implicated in a variety of physiological cellular functions, such as intracellular protein trafficking, cytoskeletal dynamics, chemotaxis of leukocytes and cell proliferation. The catalytic (HKD) and regulatory (PH and PX) domains were studied in detail in the PLD1 isoform, but PLD2 was traditionally studied in lesser detail and much less was known about its regulation. Our laboratory has been focusing on the study of PLD2 regulation in mammalian cells. Over the past few years, we have reported, in regards to the catalytic action of PLD, that PA is a chemoattractant agent that binds to and signals inside the cell through the ribosomal S6 kinases (S6K). Regarding the regulatory domains of PLD2, we have reported the discovery of the PLD2 interaction with Grb2 via Y169 in the PX domain, and further association to Sos, which results in an increase of de novo DNA synthesis and an interaction (also with Grb2) via the adjacent residue Y179, leading to the regulation of cell ruffling, chemotaxis and phagocytosis of leukocytes. We also review the complex regulation by tyrosine phosphorylation by epidermal growth factor receptor (EGF-R), Janus Kinase 3 (JAK3) and Src and the role of phosphatases. Recently, there is evidence supporting a new level of regulation of PLD2 at the PH domain, by the discovery of CRIB domains and a Rac2-PLD2 interaction that leads to a dual (positive and negative) effect on its enzymatic activity. Lastly, we review the surprising finding of PLD2 acting as a GEF. A phospholipase such as PLD that exists already in the cell membrane that acts directly on Rac allows a quick response of the cell without intermediary signaling molecules. This provides only the latest level of PLD2 regulation in a field that promises newer and exciting advances in the next few years.
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影响因子：
2.2
作者：
Blum, JJ;Lehman, JA;Gomez-Cambronero, J
通讯作者：
Gomez-Cambronero, J
DOI：
10.1083/jcb.138.3.495
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen YG;Siddhanta A;Austin CD;Hammond SM;Sung TC;Frohman MA;Morris AJ;Shields D
通讯作者：
Shields D
影响因子：
4.4
作者：
Choi, WS;Kim, YM;Beaven, MA
通讯作者：
Beaven, MA
影响因子：
3.3
作者：
Chae, Young Chan;Kim, Jung Hwan;Ryu, Sung Ho
通讯作者：
Ryu, Sung Ho
影响因子：
3.3
作者：
Block, Ethan R.;Klarlund, Jes K.
通讯作者：
Klarlund, Jes K.