A role for the actin cytoskeleton in the hormonal and growth-factor-mediated activation of protein kinase B.
A role for the actin cytoskeleton in the hormonal and growth-factor-mediated activation of protein kinase B.
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肌动蛋白细胞骨架在激素和生长因子介导的蛋白激酶 B 激活中的作用。
DOI：
10.1042/bj3520617
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
H. Hundal
中科院分区：
文献类型：
--
作者：
K. Peyrollier;E. Hajduch;A. Gray;G. Litherland;A. Prescott;N. Leslie;H. Hundal
我们在这里表明，细胞松弛素D诱导的肌动蛋白丝解聚显着减少刺激依赖性激活的蛋白激酶B（PKB）在四种不同的细胞类型（HEK-293细胞，L 6肌管，3 T3-L1脂肪细胞和U87 MG细胞）。表达PKB的普列克底物蛋白同源（PH）结构域和与绿色荧光蛋白（GFP）融合的磷酸肌醇-1（GRP 1）的一般受体的HEK-293细胞用于监测质膜中3-磷酸肌醇的产生。肌动蛋白细胞骨架的降解显著减少了胰岛素介导的PKB-PH-GFP和GRP 1-PH-GFP向质膜的易位，这与3-磷酸肌醇合成减少一致。肌动蛋白解聚不影响激素激活的磷酸肌醇3-激酶（PI 3-激酶），由于细胞松弛素D治疗也导致减少血小板衍生生长因子（PDGF）诱导的PKB磷酸化在U87 MG细胞，PTEN（磷酸酶和张力蛋白同源物删除染色体10）空细胞系，脂质磷酸酶活性不太可能占任何减少细胞3-磷酸肌醇。撤出细胞松弛素D从细胞外介质诱导肌动蛋白丝的再聚合，并恢复了招聘的PH-GFP融合蛋白的质膜和PKB激活响应于胰岛素和PDGF。我们的研究结果表明，一个完整的肌动蛋白网络是一个至关重要的要求PI 3-激酶介导的生产3-磷酸肌醇，因此，激活PKB。
We show here that cytochalasin D-induced depolymerization of actin filaments markedly reduces the stimulus-dependent activation of protein kinase B (PKB) in four different cell types (HEK-293 cells, L6 myotubes, 3T3-L1 adipocytes and U87MG cells). HEK-293 cells expressing the pleckstrin homology (PH) domains of PKB and general receptor for phosphoinositides-1 (GRP1) fused to green fluorescent protein (GFP) were used to monitor production of 3-phosphoinositides in the plasma membrane. Disassembly of the actin cytoskeleton significantly reduced the insulin-mediated translocation of both PKB-PH-GFP and GRP1-PH-GFP to the plasma membrane, consistent with diminished synthesis of 3-phosphoinositides. Actin depolymerization did not affect the hormonal activation of phosphoinositide 3-kinase (PI 3-kinase), and since cytochalasin D treatment also led to reduced platelet-derived growth factor (PDGF)-induced phosphorylation of PKB in U87MG cells, a PTEN (phosphatase and tensin homologue deleted on chromosome 10) null cell line, lipid phosphatase activity was unlikely to account for any reduction in cellular 3-phosphoinositides. Withdrawal of cytochalasin D from the extracellular medium induced actin filament repolymerization, and reinstated both the recruitment of PH-GFP fusion proteins to the plasma membrane and PKB activation in response to insulin and PDGF. Our findings indicate that an intact actin network is a crucial requirement for PI 3-kinase-mediated production of 3-phosphoinositides and, therefore, for the activation of PKB.
影响因子：
4
作者：
Z. Khayat;P. Tong;Karen Yaworsky;Robert J. Bloch;Amira Klip
通讯作者：
Z. Khayat;P. Tong;Karen Yaworsky;Robert J. Bloch;Amira Klip
邻位巯基参与 3T3-L1 脂肪细胞胰岛素激活的己糖转运的证据。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Frost,SC;Lane,MD
通讯作者：
Lane,MD