Biphasic regulation of extracellular signal-regulated kinases by scalaradial, a secretory phospholipase A(2) inhibitor
文献类型：期刊论文
| 作者 | Xie, Yili; Yu, Zhiguo; Liu, Lunhua; Guo, Yuewei ; Lou, Liguang
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| 刊名 | CANCER BIOLOGY & THERAPY
 |
| 出版日期 | 2006-08 |
| 卷号 | 5期号:8页码:988-992 |
| 关键词 | Akt arachidonic acid extracellular signal-regulated kinases phospholipase A(2) Raf-1 scalaradial |
| ISSN号 | 1538-4047 |
| DOI | 10.4161/cbt.5.8.2884 |
| 文献子类 | Article |
| 英文摘要 | The marine natural product scalaradial (SLD) is a potent inhibitor of secretary phospholipase A(2) (sPLA(2)). Our previous work has demonstrated that SLD inhibits epidermal growth factor receptor-mediated Akt phosphorylation, and this effect is independent of sPLA(2). Here we report the role of SLD in extracellular signal-regulated kinase (ERK) 1/2 activation. SLD inhibited ERK 1/2 phosphorylation within the first 15 min (early inhibition), then stimulated ERK1/2 phosphorylation after 15 min of SLD treatment (late stimulation) in BEL-7402 cells, displaying biphasic regulatory features. Other PLA(2) inhibitors such as the cytosolic and Ca2+-independent PLA(2) inhibitor methyl arachidonyl fluorophosphonate, and another sPLA(2) inhibitor, thioetheramide-phosphatidylcholine, only transiently inhibited ERK1/2 phosphorylation and did not display the stimulatory effect. The early inhibition of ERK1/2 phosphorylation by SLD was reversed by the PLA2 metabolite arachidonic acid, while the late stimulation was abrogated by constitutively active myristolated-Akt. Furthermore, SLD dose- and time-dependently inhibited the phosphorylation of Raf-1 on Ser 259, which is an established event by which Akt inhibits ERK1/2 activation. Taken together, these data demonstrate a biphasic regulation of ERK1/2 phosphorylation by SLD in a time-dependent manner, i.e., early inhibition and late stimulation. The early inhibition of ERK1/2 phosphorylation is mediated by sPLA(2), at least in part, and the late stimulation is effected through SLD inhibition of Akt. These findings provide further insight into the mechanisms underlying the pharmacological effect of SLD. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; EPIDERMAL-GROWTH-FACTOR ; SMOOTH-MUSCLE CELLS ; PHOSPHOINOSITIDE 3-KINASE ; LYSOPHOSPHATIDIC ACID ; ARACHIDONIC-ACID ; ANGIOTENSIN-II ; AKT ; PHOSPHORYLATION ; PATHWAY |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000242400700025 |
| 出版者 | LANDES BIOSCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273525]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Lou, Liguang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Yili,Yu, Zhiguo,Liu, Lunhua,et al. Biphasic regulation of extracellular signal-regulated kinases by scalaradial, a secretory phospholipase A(2) inhibitor[J]. CANCER BIOLOGY & THERAPY,2006,5(8):988-992. |
| APA | Xie, Yili,Yu, Zhiguo,Liu, Lunhua,Guo, Yuewei,&Lou, Liguang.(2006).Biphasic regulation of extracellular signal-regulated kinases by scalaradial, a secretory phospholipase A(2) inhibitor.CANCER BIOLOGY & THERAPY,5(8),988-992. |
| MLA | Xie, Yili,et al."Biphasic regulation of extracellular signal-regulated kinases by scalaradial, a secretory phospholipase A(2) inhibitor".CANCER BIOLOGY & THERAPY 5.8(2006):988-992. |
入库方式： OAI收割
来源：上海药物研究所
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