The Cdk5/p35 kinases modulate leptin-induced STAT3 signaling.
The Cdk5/p35 kinases modulate leptin-induced STAT3 signaling.
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DOI：
10.1007/s12031-008-9174-3
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Pan W
中科院分区：
文献类型：
--
作者：
He Y;Kastin AJ;Hsuchou H;Pan W
细胞周期蛋白依赖性激酶（Cdk）-5在脑中广泛表达，并且在CNS发育和突触可塑性中起重要作用。p35激酶是Cdk 5的神经元特异性激活剂。在这里，我们首次表明Cdk 5激活调节瘦素信号。P35及其代谢产物p25与瘦素受体ObR共定位于下丘脑的选择性神经元中。在细胞模型中，p35单独过表达足以诱导信号转导子和转录激活子3（STAT 3）的转录激活。在视黄酸分化的SH-SY 5 Y神经元细胞中，ObRb诱导，瘦素增加Cdk 5，p35和p25激酶的表达。诱导的时间过程与磷酸化（p）-STAT 3的时间过程一致。当Cdk 5活性被抑制，无论是由roscovitine或显性负Cdk 5的过表达，有减少pSTAT 3激活。结果表明，p35对Cdk 5的激活在3 ~ 6 h内维持了瘦素诱导的pSTAT 3。因此，p35是瘦素诱导的STAT 3信号转导的新调节剂。
Cyclin dependent kinase (Cdk)-5 is ubiquitously expressed in the brain and plays an essential role in CNS development and synaptic plasticity. The p35 kinase is a neuronal specific activator of Cdk5. Here, we show for the first time that Cdk5 activation modulates leptin signaling. P35 and its metabolite p25 were co-localized with the leptin receptor ObR in selective neurons in the hypothalamus. Overexpression of p35 alone was sufficient to induce the transcriptional activation of Signal Transducer and Activator of Transcription 3 (STAT3) in a cellular model. In retinoic acid-differentiated SH-SY5Y neuronal cells where ObRb was induced, leptin increased the expression of Cdk5, p35, and p25 kinases. The time course of induction coincided with that of phosphorylated (p)-STAT3. When Cdk5 activity was inhibited, either by roscovitine or overexpression of dominant negative Cdk5, there was a reduction of pSTAT3 activation. The results show that the activation of Cdk5 by p35 sustained leptin-induced pSTAT3 at 3 – 6 h. Thus, p35 is a novel modulator of leptin-induced STAT3 signaling.
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DOI：
10.1111/j.1432-1033.1997.t01-2-00527.x
发表时间：
1997-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Meijer, L;Borgne, A;Moulinoux, JP
通讯作者：
Moulinoux, JP
影响因子：
4.8
作者：
Lin, Ho;Chen, Mei-Chih;Lin, Shih-Yi
通讯作者：
Lin, Shih-Yi
DOI：
10.1073/pnas.89.22.10867
发表时间：
1992-11-15
影响因子：
11.1
作者：
HELLMICH, MR;PANT, HC;BATTEY, JF
通讯作者：
BATTEY, JF
影响因子：
4.8
作者：
Pan, Weihong;Hsuchou, Hung;Kastin, Abba J.
通讯作者：
Kastin, Abba J.
影响因子：
4.8
作者：
Pan, Weihong;Hsuchou, Hung;Kastin, Abba J.
通讯作者：
Kastin, Abba J.