Platelet-Derived Growth Factor Stimulates Phospholipase C-γ1, Extracellular Signal-Regulated Kinase, and Arachidonic Acid Release in Rat Myometrial Cells: Contribution to Cyclic 3′,5′-Adenosine Monophosphate Production and Effect on Cell Proliferation1
Platelet-Derived Growth Factor Stimulates Phospholipase C-γ1, Extracellular Signal-Regulated Kinase, and Arachidonic Acid Release in Rat Myometrial Cells: Contribution to Cyclic 3′,5′-Adenosine Monophosphate Production and Effect on Cell Proliferation1
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血小板衍生生长因子刺激大鼠子宫肌细胞中磷脂酶 C-γ1、细胞外信号调节激酶和花生四烯酸释放：对环状 3,5-单磷酸腺苷产生的贡献以及对细胞增殖的影响1
作者：
Isaline Boulven;B. Palmier;P. Robin;M. Vacher;S. Harbon;D. Leiber
摘要在本研究中，我们研究了培养的大鼠子宫肌层细胞暴露于血小板衍生生长因子（PDGF）后的下游信号事件及其对细胞增殖的影响。PDGF-BB诱导PDGF-β受体的酪氨酸磷酸化，并通过磷脂酶（PL）C-γ1的酪氨酸磷酸化增加三磷酸肌醇的产生。PDGF-BB还增加cAMP的合成。这种增加由毛喉素增强，并由吲哚美辛（一种环氧合酶抑制剂）降低，反映了通过前列腺素生物合成的Gs蛋白介导的过程。PDGF产生的前列腺素被表征为前列环素（PGI 2）。PDGF-BB增加花生四烯酸（AA）的释放，这类似于cAMP的积累，被废除的存在下，AACOCF 3，一种胞质PLA 2抑制剂，在Ca 2+的情况下。U-73122是一种有效的PLC活性抑制剂，可阻断磷酸肌醇的产生和PDGF-BB引发的AA释放。细胞外信号调节激酶（ERK）1和2在子宫肌层细胞中表达，PDGF-BB选择性激活ERK 2。ERK激活激酶抑制剂PD 98059阻断PDGF-BB介导的ERK 2激活、AA释放和cAMP产生。结果表明，PDGF-BB通过PLC激活和ERK依赖的AA释放和PGI 2生物合成刺激cAMP形成。PDGF-BB还增加细胞增殖和[3 H]胸苷掺入。这被PD 98059消除，表明ERK级联是PDGF-BB的促有丝分裂作用所必需的。毛喉素，加强cAMP对PDGF-BB的反应，减弱PDGF-BB触发的DNA合成和ERK激活，表明存在负反馈调节。
Abstract In the present study, we examined downstream signaling events that followed exposure of cultured rat myometrial cells to platelet-derived growth factor (PDGF) and their effect on cell proliferation. PDGF-BB induced tyrosine phosphorylation of PDGF-β receptors and increased inositol trisphosphate production via the tyrosine phosphorylation of phospholipase (PL)C-γ1. PDGF-BB also increased cAMP synthesis. This increase was potentiated by forskolin and reduced by indomethacin, a cyclooxygenase inhibitor, reflecting a Gs protein-mediated process via prostaglandin biosynthesis. The prostaglandin produced by PDGF was characterized as prostacyclin (PGI2). PDGF-BB increased arachidonic acid (AA) release, which, similarly to cAMP accumulation, was abolished in the presence of AACOCF3, a cytosolic PLA2 inhibitor, and in the absence of Ca2+. U-73122, a potent inhibitor of PLC activity, blocked both the production of inositol phosphates and the AA release triggered by PDGF-BB. Extracellular signal-regulated kinases (ERKs) 1 and 2 are expressed in myometrial cells, and PDGF-BB selectively activated ERK2. PD98059, an inhibitor of the ERK-activating kinase, blocked PDGF-BB-mediated ERK2 activation, AA release, and cAMP production. The results demonstrate that PDGF-BB stimulated cAMP formation through both PLC activation and ERK-dependent AA release and PGI2 biosynthesis. PDGF-BB also increased cell proliferation and [3H]thymidine incorporation. This was abolished by PD98059, demonstrating that the ERK cascade is required for the mitogenic effect of PDGF-BB. Forskolin, which potentiated the cAMP response to PDGF-BB, attenuated both DNA synthesis and ERK activation triggered by PDGF-BB, suggesting the presence of a negative feedback regulation.
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DOI：
10.1073/pnas.90.21.10300
发表时间：
1993-11-01
影响因子：
11.1
作者：
GRAVES, LM;BORNFELDT, KE;KREBS, EG
通讯作者：
KREBS, EG
85-kDa 磷脂酶 A2 的紧密结合抑制剂（而非 14-kDa 磷脂酶 A2）可抑制凝血酶刺激的人血小板中游离花生四烯酸的释放。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bartoli,F;Lin,HK;Ghomashchi,F;Gelb,MH;Jain,MK;Apitz-Castro,R
通讯作者：
Apitz-Castro,R
DOI：
10.1172/jci118546
发表时间：
1996-03
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Michael Mingzhao Xing;P. Insel
通讯作者：
Michael Mingzhao Xing;P. Insel
影响因子：
4.8
作者：
C. Ku;Ansha Qian;Yeshao Wen;Khursheed Anwer;Barbara M. Sanborn
通讯作者：
C. Ku;Ansha Qian;Yeshao Wen;Khursheed Anwer;Barbara M. Sanborn
影响因子：
56.9
作者：
COOK, SJ;MCCORMICK, F
通讯作者：
MCCORMICK, F