A novel role for PTK2B in cultured beige adipocyte differentiation
A novel role for PTK2B in cultured beige adipocyte differentiation
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DOI：
10.1016/j.bbrc.2018.05.021
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发表时间：
2018-07-02
影响因子：
3.1
通讯作者：
Celi, Francesco S.
中科院分区：
文献类型：
--
作者：
Ni, Bin;Farrar, Jared S.;Celi, Francesco S.
脂肪细胞分化是一个严格调控的过程，需要大量基因和蛋白质的有序表达。胞质蛋白和关键转录因子的磷酸化代表了导致脂肪细胞成熟和调节相关代谢途径的过程的关键调节机制。尽管认识到蛋白质磷酸化在脂肪细胞生物学中的重要性，但对特定激酶在产热（棕色或米色）脂肪细胞分化和功能中的作用知之甚少。在这项研究中，我们证明了非受体蛋白酪氨酸激酶2 β（PTK 2B）在小鼠米色脂肪细胞分化中起着关键作用。我们观察到PTK 2B蛋白表达与培养的、永生化的腹股沟基质血管部分细胞中的米色脂肪细胞分化相关。CRISPR/Cas9介导的Ptk 2b敲除导致非分化的白色脂肪细胞和分化的米色脂肪细胞，其具有显著降低的产热基因和蛋白质表达、增大的脂滴尺寸和改变的线粒体呼吸。总之，我们在细胞培养系统中的数据为PTK 2B在鼠米色脂肪细胞分化中的作用提供了证据。(C)2018爱思唯尔公司All rights reserved.
Adipocyte differentiation is a tightly regulated process which requires the sequential and organized expression of numerous genes and proteins. Phosphorylation of cytoplasmic proteins and key transcription factors represents a critical regulatory mechanism of the process leading to adipocyte maturation and modulation of associated metabolic pathways. Despite the recognition of the importance of protein phosphorylation in adipocyte biology, relatively little is known about the role of specific kinases in thermogenic (brown or beige) adipocyte differentiation and function. In this study, we demonstrate that the non-receptor protein tyrosine kinase 2 beta (PTK2B) plays a critical role in murine beige adipocyte differentiation. We observed that PTK2B protein expression is associated with beige adipocyte differentiation in cultured, immortalized, inguinal stromal vascular fraction cells. CRISPR/Cas9-mediated knock-out of Ptk2b results in non-differentiating white adipocytes, and differentiated beige adipocytes with significantly reduced thermogenic gene and protein expression, enlarged lipid droplet size, and altered mitochondrial respiration. Together, our data in a cell culture system provides evidence for a role of PTK2B in the differentiation of murine beige adipocytes. (C) 2018 Elsevier Inc. All rights reserved.