Differential signaling during macropinocytosis in response to M-CSF and PMA in macrophages.
Differential signaling during macropinocytosis in response to M-CSF and PMA in macrophages.
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巨噬细胞中对M-CSF和PMA的大型细胞增多症期间的差异信号传导。
DOI：
10.3389/fphys.2015.00008
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发表时间：
2015
影响因子：
4
通讯作者：
Swanson JA
中科院分区：
文献类型：
--
作者：
Yoshida S;Gaeta I;Pacitto R;Krienke L;Alge O;Gregorka B;Swanson JA
构成大胞饮体的细胞运动在质膜的杯状区域中具有相应的化学转变序列，该区域成为大胞饮体。为了确定I型磷脂酰肌醇3-激酶（PI 3 K）和磷脂酶C（PLC）在这一途径中的相对位置，我们分析了巨噬细胞巨噬细胞集落刺激因子（M-CSF）和二酰基甘油（DAG）类似物佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）刺激的巨噬细胞巨胞饮。在用M-CSF刺激的细胞中，细胞内脂质的荧光探针的显微成像表明，PI 3 K产物磷脂酰肌醇（3，4，5）-三磷酸（PIP 3）在DAG之前出现在杯中。然后，我们测试的假设，PMA和DAG的功能后，PI 3 K和Ras和蛋白激酶C（PKC）在巨噬细胞巨胞饮体形成之前。尽管M-CSF激活了PI 3 K靶点Akt，但Akt抑制剂MK-2206不抑制巨胞饮。磷脂酶C（PLC）抑制剂U 73122阻断M-CSF的巨胞饮作用，但不阻断PMA。Ras抑制剂法呢基硫代水杨酸酯（FTS），PKC抑制剂Calphostin C和广泛特异性抑制剂rottlerin抑制M-CSF和PMA的巨胞饮反应。这些研究支持了一种模型，其中M-CSF刺激巨胞饮杯中的PI 3 K，并且由此产生的PIP 3的增加激活PLC，PLC进而产生激活PKC、Ras和巨胞饮体关闭的晚期所必需的DAG。
The cellular movements that construct a macropinosome have a corresponding sequence of chemical transitions in the cup-shaped region of plasma membrane that becomes the macropinosome. To determine the relative positions of type I phosphatidylinositol 3-kinase (PI3K) and phospholipase C (PLC) in this pathway, we analyzed macropinocytosis in macrophages stimulated by the growth factor macrophage-colony-stimulating factor (M-CSF) and by the diacylglycerol (DAG) analog phorbol 12-myristate 13-acetate (PMA). In cells stimulated with M-CSF, microscopic imaging of fluorescent probes for intracellular lipids indicated that the PI3K product phosphatidylinositol (3,4,5)-trisphosphate (PIP3) appeared in cups just prior to DAG. We then tested the hypothesis that PMA and DAG function after PI3K and prior to Ras and protein kinase C (PKC) during macropinosome formation in macrophages. Although the PI3K target Akt was activated by M-CSF, the Akt inhibitor MK-2206 did not inhibit macropinocytosis. The phospholipase C (PLC) inhibitor U73122 blocked macropinocytosis by M-CSF but not PMA. Macropinocytosis in response to M-CSF and PMA was inhibited by the Ras inhibitor farnesyl thiosalicylate (FTS), by the PKC inhibitor Calphostin C and by the broad specificity inhibitor rottlerin. These studies support a model in which M-CSF stimulates PI3K in macropinocytic cups, and the resulting increase in PIP3 activates PLC, which in turn generates DAG necessary for activation of PKC, Ras and the late stages of macropinosome closure.
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影响因子：
3.7
作者：
Haspot F;Lavault A;Sinzger C;Laib Sampaio K;Stierhof YD;Pilet P;Bressolette-Bodin C;Halary F
通讯作者：
Halary F
影响因子：
9.8
作者：
Beemiller P;Hoppe AD;Swanson JA
通讯作者：
Swanson JA
影响因子：
56.9
作者：
Franke, TF;Kaplan, DR;Toker, A
通讯作者：
Toker, A
影响因子：
11.4
作者：
Falasca, M;Logan, SK;Schlessinger, J
通讯作者：
Schlessinger, J
影响因子：
3.3
作者：
Amyere, M;Payrastre, B;Courtoy, PJ
通讯作者：
Courtoy, PJ