Role of the SIK2-p35-PJA2 complex in pancreatic β-cell functional compensation.
Role of the SIK2-p35-PJA2 complex in pancreatic β-cell functional compensation.
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SIK2-P35-PJA2复合物在胰腺β细胞功能补偿中的作用。
DOI：
10.1038/ncb2919
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发表时间：
2014-03
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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作者：
Energy sensing by the AMP-activated protein kinase (AMPK) is of fundamental importance in cell biology. In the pancreatic beta cell, AMPK is a central regulator of insulin secretion. The capacity of the beta cell to increase insulin output is a critical compensatory mechanism in prediabetes, yet its molecular underpinnings are unclear. Here we delineate a complex consisting of the AMPK-related kinase SIK2, the CDK5 activator CDK5R1/p35, and the E3 ligase PJA2 essential for beta cell functional compensation. Following glucose stimulation, SIK2 phosphorylates p35 at Ser91, to trigger its ubiquitination via PJA2 and promote insulin secretion. Furthermore SIK2 accumulates in beta cells in models of metabolic syndrome to permit compensatory secretion; in contrast, beta cell knockout of SIK2 leads to accumulation of p35 and impaired secretion. This work demonstrates that the SIK2-PJA2-p35 complex is essential for glucose homeostasis and provides a link between p35-CDK5 and the AMPK family in excitable cells.
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影响因子：
50.3
作者：
Ahmed AA;Lu Z;Jennings NB;Etemadmoghadam D;Capalbo L;Jacamo RO;Barbosa-Morais N;Le XF;Australian Ovarian Cancer Study Group;Vivas-Mejia P;Lopez-Berestein G;Grandjean G;Bartholomeusz G;Liao W;Andreeff M;Bowtell D;Glover DM;Sood AK;Bast RC Jr
通讯作者：
Bast RC Jr
影响因子：
4.8
作者：
Liu, Ying;Poon, Victoria;Aguilera, Greti
通讯作者：
Aguilera, Greti
DOI：
10.1152/ajpendo.1996.270.4.e572
发表时间：
1996-04-01
影响因子：
5.1
作者：
Byrne, MM;Sturis, J;Polonsky, KS
通讯作者：
Polonsky, KS
DOI：
10.1073/pnas.0900218106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Lalioti, Vasiliki;Muruais, Gemma;Sandoval, Ignacio V.
通讯作者：
Sandoval, Ignacio V.
影响因子：
21.3
作者：
Lignitto, Luca;Carlucci, Annalisa;Feliciello, Antonio
通讯作者：
Feliciello, Antonio