Protein phosphatase 3 differentially modulates vascular endothelial growth factor- and fibroblast growth factor 2-stimulated cell proliferation and signaling in ovine fetoplacental artery endothelial cells.
Protein phosphatase 3 differentially modulates vascular endothelial growth factor- and fibroblast growth factor 2-stimulated cell proliferation and signaling in ovine fetoplacental artery endothelial cells.
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蛋白质磷酸酶3差异调节血管内皮生长因子和成纤维细胞生长因子2刺激细胞增殖和卵巢胎儿动脉内皮细胞的信号传导。
DOI：
10.1095/biolreprod.108.068957
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发表时间：
2008-10
影响因子：
3.6
通讯作者：
Zheng, Jing
中科院分区：
文献类型：
--
作者：
Wang, Kai;Song, Yang;Chen, Dong-Bao;Zheng, Jing
关键词：
血管内皮生长因子（VEGF）和成纤维细胞生长因子2（FGF 2）调节细胞功能的一个关键过程是可逆的蛋白磷酸化，它受到蛋白激酶和磷酸酶平衡的严格控制。我们已经报道，在绵羊胎儿胎盘动脉内皮（OFPAE）细胞，VEGF和FGF 2刺激细胞增殖，部分通过激活丝裂原活化蛋白激酶激酶1/2（MAP 2K 1/2）/丝裂原活化蛋白激酶3/1（MAPK 3/1）和磷酸肌醇3-激酶（PI 3 K）/v-akt小鼠胸腺瘤病毒癌基因同源物1（AKT 1）途径。在这项研究中，我们研究了蛋白磷酸酶3（PPP 3）介导的VEGF和FGF 2通过调节MAPK 3/1和AKT 1的激活来刺激OFPAE细胞增殖。应用针对人PPP 3催化亚基α（PPP 3CA）的小干扰RNA（siRNA）抑制PPP 3CA蛋白在OFPAE细胞中的表达。与乱序siRNA相比，PPP 3CA siRNA使PPP 3CA蛋白水平降低约97%，而不改变蛋白磷酸酶2（PPP 2）催化亚基α（PPP 2CA）、总MAPK 3/1、总AKT 1或甘油醛-3-磷酸脱氢酶（GAPDH）的蛋白水平。敲低PPP 3CA蛋白表达增强VEGF刺激的细胞增殖，但不增强FGF 2刺激的细胞增殖。PPP 3CA蛋白表达的敲低并不显著影响VEGF诱导的MAPK 3/1和AKT 1磷酸化，而减弱FGF 2诱导的MAPK 3/1和AKT 1磷酸化。因此，这是第一个报告证明成功敲低PPP 3CA蛋白表达在任何细胞模型中使用一对双应变siRNA。此外，PPP 3CA蛋白表达的特异性敲除增强VEGF刺激的OFPAE细胞增殖，而不是FGF 2刺激的OFPAE细胞增殖，并减弱FGF 2诱导的MAPK 3/1和AKT 1活化，而不是VEGF诱导的MAPK 3/1和AKT 1活化。因此，PPP 3CA差异调节VEGF和FGF 2刺激的细胞增殖和OFPAE细胞中的信号级联。这些数据还表明，在OFPAE细胞中PPP 3CA敲低后，MAPK 3/1和AKT 1以外的信号分子在VEGF和FGF 2刺激的细胞增殖中起重要作用。
A critical process for vascular endothelial growth factor (VEGF)- and fibroblast growth factor 2 (FGF2)-regulated cellular function is reversible protein phosphorylation, which is tightly controlled by a balance of protein kinases and phosphatases. We have reported that in ovine fetoplacental artery endothelial (OFPAE) cells, VEGF and FGF2 stimulate cell proliferation partially via activation of mitogen-activated protein kinase kinase 1/2 (MAP2K1/2)/mitogen-activated protein kinase 3/1 (MAPK3/1) and phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogen homolog 1 (AKT1) pathways. In this study, we examined if protein phosphatase 3 (PPP3) mediated VEGF- and FGF2-stimulated OFPAE cell proliferation via modulating activation of MAPK3/1 and AKT1. Small interfering RNA (siRNA) targeting human PPP3 catalytic subunit α (PPP3CA) was used to suppress PPP3CA protein expression in OFPAE cells. As compared with the scrambled siRNA, PPP3CA siRNA decreased PPP3CA protein levels by ~ 97% without altering protein levels of protein phosphatase 2 (PPP2) catalytic subunit α (PPP2CA), total MAPK3/1, total AKT1, or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Knockdown of PPP3CA protein expression enhanced VEGF-, but not FGF2-stimulated cell proliferation. Knockdown of PPP3CA protein expression did not significantly affect VEGF-induced MAPK3/1 and AKT1 phosphorylation, while attenuated FGF2-induced MAPK3/1 and AKT1 phosphorylation. Thus, this is the first report demonstrating successful knockdown of PPP3CA protein expression in any cell model using a single pair of double-strained siRNA. Moreover, specific knockdown of PPP3CA protein expression enhances VEGF-, but not FGF2-stimulated OFPAE cell proliferation and attenuates FGF2-, but not VEGF-induced MAPK3/1 and AKT1 activation. Thus, PPP3CA differentially modulates the VEGF- and FGF2-stimulated cell proliferation and signaling cascades in OFPAE cells. These data also suggest that signaling molecules other than MAPK3/1 and AKT1 play an important role in VEGF- and FGF2-stimulated cell proliferation after knockdown of PPP3CA in OFPAE cells.
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DOI：
10.1186/1478-811x-2-3
发表时间：
2004-06-02
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Rafiee P;Heidemann J;Ogawa H;Johnson NA;Fisher PJ;Li MS;Otterson MF;Johnson CP;Binion DG
通讯作者：
Binion DG
影响因子：
19.6
作者：
Kiely, B;Feldman, G;Ryan, MP
通讯作者：
Ryan, MP
影响因子：
3.5
作者：
COHEN, PTW;BREWIS, ND;MANN, DJ
通讯作者：
MANN, DJ
影响因子：
64.5
作者：
Graef, IA;Chen, F;Crabtree, GR
通讯作者：
Crabtree, GR
环孢菌素 A 通过 MAPK/ERK 信号传导诱导肌联蛋白表达，并提高人滋养层细胞的增殖和侵袭潜力
影响因子：
6.1
作者：
Du, Mei-Rong;Zhou, Wen-Hui;Li, Da-Jin
通讯作者：
Li, Da-Jin