TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha.
TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha.
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DOI：
10.1016/j.bbrc.2010.07.126
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发表时间：
2010-09-10
影响因子：
3.1
通讯作者：
Yin, Fei
中科院分区：
文献类型：
--
作者：
Yang, Lifen;Qiao, Guilin;Ying, Haiyan;Zhang, Jian;Yin, Fei
Akt信号在T细胞增殖、凋亡和调节性T细胞发育等功能中起着核心作用。疏水基序Ser473位点及其激活环Thr308位点的磷酸化被认为是Akt功能的必要条件。磷酸化肌醇依赖激酶1 （Phosphoinositide-dependent kinase 1, PDK-1）磷酸化Akt的Thr308位点，但磷酸化Akt的Ser473位点的激酶（PDK-2）仍不清楚。PDK-2的存在被认为是特定于细胞类型和刺激的。T细胞中PDK-2对TCR刺激的反应尚未明确定义。在本研究中，我们发现传统PKC正调控tcr诱导的Akt Ser473磷酸化。从T细胞中纯化的pkc - α在体外TCR刺激下可磷酸化Akt的Ser473位点。在T细胞系Jurkat细胞中敲低pkc - α可减少tcr诱导的Akt及其下游靶点的磷酸化。因此，我们的研究结果表明，pkc - α是TCR刺激下T细胞中PDK-2的候选者。
Akt signaling plays a central role in T cell functions, such as proliferation, apoptosis, and regulatory T cell development. Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function. It is widely accepted that Phosphoinositide-dependent kinase 1 (PDK-1) phosphorylates Akt at Thr308, but the kinase(s) responsible for phosphorylating Akt at Ser473 (PDK-2) remains elusive. The existence of PDK-2 is considered to be specific to cell type and stimulus. PDK-2 in T cells in response to TCR stimulation has not been clearly defined. In this study, we found that conventional PKC positively regulated TCR-induced Akt Ser473 phosphorylation. PKC-alpha purified from T cells can phosphorylate Akt at Ser473 in vitro upon TCR stimulation. Knockdown of PKC-alpha in T cell line Jurkat cells reduced TCR-induced phosphorylation of Akt as well as its downstream targets. Thus our results suggest that PKC-alpha is a candidate for PDK-2 in T cells upon TCR stimulation.
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DOI：
10.1073/pnas.0800928105
发表时间：
2008-06-03
影响因子：
11.1
作者：
Sauer, Stephan;Bruno, Ludovica;Merkenschlager, Matthias
通讯作者：
Merkenschlager, Matthias
影响因子：
64.8
作者：
Carlson, Corey M.;Endrizzi, Bart T.;Jameson, Stephen C.
通讯作者：
Jameson, Stephen C.
影响因子：
4.4
作者：
Mao, Changchuin;Tili, Esmerina G.;Tsichlis, Philip N.
通讯作者：
Tsichlis, Philip N.
影响因子：
7.5
作者：
Bozulic, Lana;Hemmings, Brian A.
通讯作者：
Hemmings, Brian A.
影响因子：
3.5
作者：
Gschwendt, M;Dieterich, S;Johannes, FJ
通讯作者：
Johannes, FJ