New concepts in phospholipase D signaling in inflammation and cancer.
New concepts in phospholipase D signaling in inflammation and cancer.
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DOI：
10.1100/tsw.2010.116
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发表时间：
2010-07-07
影响因子：
--
通讯作者：
Gomez-Cambronero J
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文献类型：
--
作者：
Gomez-Cambronero J
磷脂酶D（PLD）催化磷脂酰胆碱水解产生脂质第二信使磷脂酸（PA）和胆碱。细胞中PLD的调节福尔斯分为两个主要的信号传导类别。一种是通过生长因子/有丝分裂原，如EGF、PDGF、胰岛素和血清，并涉及酪氨酸激酶;另一种是通过小GT3蛋白Arf和Rho。我们在这里总结了我们实验室和其他小组对这些途径的贡献，并介绍了几个新的概念。对于丝裂原诱导的信号传导，新的数据表明，在PLD 2过表达细胞中细胞转化的增加是由于PLD 2诱导的从头DNA合成的增加，其中参与这些功能的特定酪氨酸残基是Y和Y。最近的研究还表明Grb 2参与了PLD 2的酪氨酸磷酸化，这也涉及Sos和ERK通路。最近已精确绘制了PLD 2分子内对其调节至关重要的磷酸化靶点。它们是Y、Y和Y，负责的激酶分别是EGFR、JAK 3和Src。Y是一个抑制位点，其磷酸化解释了低侵袭性MCF-7乳腺癌细胞中存在的低PLD 2活性。沿着小GT酶前沿的进展涉及细胞迁移，因为PLD 1和PLD 2引起白细胞趋化性和炎症的增加。PA是完全趋化性所必需的。PA在极化中性粒细胞的前沿富集非典型鸟嘌呤交换因子（GEF）DOCK 2的定位。此外，细胞外PA作为嗜中性粒细胞化学引诱物; PA进入细胞并激活mTOR/S6 K通路（特别是S6 K）。PLD与mTOR/S6 K通路之间的明确联系已经建立，因为PA与mTOR结合，并且也独立于mTOR与S6 K结合。最后，在细胞信号传导的上游方向有证据表明，mTOR和S6 K在基础条件下保持PLD 2基因表达功能下调。总之，PLD 2在细胞信号传导中的参与继续以几何级数扩展。它涉及基因转录、促有丝分裂和细胞迁移作用，如在正常生长、肿瘤发展和炎症中所见。
Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate the lipid second messenger phosphatidic acid (PA) and choline. PLD regulation in cells falls into two major signaling categories. One is via growth factors/mitogens, such as EGF, PDGF, insulin, and serum, and implicates tyrosine kinases; the other is via the small GTPase proteins Arf and Rho. We summarize here our lab's and other groups' contributions to those pathways and introduce several novel concepts. For the mitogen-induced signaling, new data indicate that an increase in cell transformation in PLD2-overexpressing cells is due to an increase of de novo DNA synthesis induced by PLD2, with the specific tyrosine residues involved in those functions being Y and Y. Recent research has also implicated Grb2 in tyrosine phosphorylation of PLD2 that also involves Sos and the ERK pathway. The targets of phosphorylation within the PLD2 molecule that are key to its regulation have recently been precisely mapped. They are Y, Y, and Y and the responsible kinases are, respectively, EGFR, JAK3, and Src. Y is an inhibitory site and its phosphorylation explains the low PLD2 activity that exists in low-invasive MCF-7 breast cancer cells. Advances along the small GTPase front have implicated cell migration, as PLD1 and PLD2 cause an increase in chemotaxis of leukocytes and inflammation. PA is necessary for full chemotaxis. PA enriches the localization of the atypical guanine exchange factor (GEF), DOCK2, at the leading edge of polarized neutrophils. Further, extracellular PA serves as a neutrophil chemoattractant; PA enters the cell and activates the mTOR/S6K pathway (specifically, S6K). A clear connection between PLD with the mTOR/S6K pathway has been established, in that PA binds to mTOR and also binds to S6K independently of mTOR. Lastly, there is evidence in the upstream direction of cell signaling that mTOR and S6K keep PLD2 gene expression function down-regulated in basal conditions. In summary, the involvement of PLD2 in cell signaling continues to expand geometrically. It involves gene transcription, mitogenic and cell migration effects as seen in normal growth, tumor development, and inflammation.
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影响因子：
7
作者：
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通讯作者：
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