PI3-kinase p85alpha is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells.
PI3-kinase p85alpha is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells.
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DOI：
10.1111/j.1349-7006.2001.tb01187.x
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发表时间：
2001-09
期刊：
影响因子：
--
通讯作者：
Kohgo Y
中科院分区：
文献类型：
--
作者：
Tanaka K;Fujimoto Y;Suzuki M;Suzuki Y;Ohtake T;Saito H;Kohgo Y
PR-39是一种内源性抗菌肽，可与NADPH复合体蛋白p47Phox和信号转导蛋白p30Cas的3个同源结构域结合。最近，我们报道了PR-39基因转导改变了人肝癌细胞的侵袭活性和肌动蛋白结构，提示PR-39多肽通过其富含Pro的基序影响细胞信号转导。为了阐明PR-39的作用机制，我们将PR-39基因导入人活化k-ras基因转化的小鼠NIH3T3细胞中。PR-39基因转染体在体内外表现出肌动蛋白结构的重组和细胞增殖的抑制。PR-39基因转染组MAP(丝裂原活化蛋白)激酶活性、细胞周期蛋白Dl表达和JNK活性均下降。免疫共沉淀分析表明，PR-39与PI3-Kp85α结合，PI3-Kp85是PI3-Kp85的调节亚基，是ras诱导细胞骨架改变和刺激有丝分裂的效应因子之一。与ras转化子相比，PR-39基因转染体的PI3-K活性降低。这些结果表明，PR-39通过与PI3-激酶P85α结合并抑制PI3-激酶活性来改变肌动蛋白结构和细胞增殖率。
PR‐39, which is an endogenous antimicrobial peptide, can bind to Src homology 3 domains of the NADPH complex protein p47phox and the signaling adapter protein p!30Cas. Recently, we have reported that PR‐39 gene transduction altered invasive activity and actin structure of human hepatocellular carcinoma cells, suggesting that this peptide affects cellular signaling due to its prolinerich motif. In order to clarify the mechanism of the PR‐39 functions, we transfected the PR‐39 gene into mouse NIH3T3 cells which had already been transformed with human activated k‐ras gene. The PR‐39 gene transfectant showed a reorganization of actin structure and suppression of cell proliferation both in vitro and in vivo. Decreases of MAP (mitogen‐activated protein) kinase activity, cyclin Dl expression and JNK activity were observed in the PR‐39 gene transfectant. Co‐immunoprecipitation analysis revealed that PR‐39 binds to PI3‐kinase p85α, which is a regulatory subunit of PI3‐kinase and one of the effectors by which ras induces cytoskeletal changes and stimulates mitogenesis. The PI3‐kinase activity of the PR‐39 gene transfectant was decreased compared with that of the ras transformant. These results suggest that PR‐39 alters actin structure and cell proliferation rate by binding to PI3‐kinase p85α and suppressing the PI3‐kinase activity.
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富含脯氨酸的抗微生物肽，PR-39基因转导改变了人肝细胞癌细胞中的侵入性活性和肌动蛋白结构。
影响因子：
8.8
作者：
Ohtake, T;Fujimoto, Y;Ikuta, K;Saito, H;Ohhira, M;Ono, M;Kohgo, Y
通讯作者：
Kohgo, Y
DOI：
10.1073/pnas.93.12.6014
发表时间：
1996-06-11
影响因子：
11.1
作者：
Shi, JS;Ross, CR;Blecha, F
通讯作者：
Blecha, F
影响因子：
10.5
作者：
MCCARTHY, SA;SAMUELS, ML;MCMAHON, M
通讯作者：
MCMAHON, M
DOI：
10.1073/pnas.91.23.11035
发表时间：
1994-11-08
影响因子：
11.1
作者：
GALLO, RL;ONO, M;BERNFIELD, M
通讯作者：
BERNFIELD, M
影响因子：
56.9
作者：
Rommel, C;Clarke, BA;Glass, DJ
通讯作者：
Glass, DJ