Jin Nana, Ma Denglei, Gu Jianlan, Shi Jianhua, Xu Xiaotao, Iqbal Khalid, Gong Cheng-Xin, Liu Fei, Chu Dandan
Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education of China, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, PR China; Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA; Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Biochem Biophys Res Commun. 2018 Feb 26;497(1):194-199. doi: 10.1016/j.bbrc.2018.02.053. Epub 2018 Feb 7.
O-GlcNAcylation is a post-translational modification of proteins. Protein kinase A (PKA)-cAMP response element binding protein (CREB) signaling plays critical roles in multiple biological processes. Isoforms α and β of PKA catalytic subunit (PKAc) and CREB are modified by O-GlcNAcylation. In the present study, we determined the role of O-GlcNAcylation in PKAc isoform-specific CREB signaling. We found that up-regulation of O-GlcNAcylation enhanced CREB phosphorylation, but suppressed CREB expression in exogenous PKAc isoform-unspecific manner. PKAc isoforms affected exogenous expression of OGT or OGA and protein O-GlcNAcylation differently. Up-regulation of O-GlcNAcylation did not significantly affect net PKAcα-CREB signaling, but enhanced PKAcβ-CREB signaling. The role of O-GlcNAcylation in PKA-CREB signaling was desensitized by insulin treatment. This study suggests a role of O-GlcNAcylation in PKA-CREB signaling by affecting phosphorylation of CREB in a PKAc isoform-specific manner.
O-连接的N-乙酰葡糖胺化（O-GlcNAcylation）是一种蛋白质的翻译后修饰。蛋白激酶A（PKA）-环磷酸腺苷反应元件结合蛋白（CREB）信号通路在多种生物学过程中发挥关键作用。PKA催化亚基（PKAc）的α和β同工型以及CREB都可被O-GlcNAcylation修饰。在本研究中，我们确定了O-GlcNAcylation在PKAc同工型特异性CREB信号通路中的作用。我们发现，O-GlcNAcylation的上调增强了CREB的磷酸化，但以外源性PKAc同工型非特异性的方式抑制了CREB的表达。PKAc同工型对外源性OGT或OGA的表达以及蛋白质O-GlcNAcylation的影响不同。O-GlcNAcylation的上调并未显著影响净PKAcα-CREB信号通路，但增强了PKAcβ-CREB信号通路。胰岛素处理使O-GlcNAcylation在PKA-CREB信号通路中的作用脱敏。本研究表明，O-GlcNAcylation通过以PKAc同工型特异性的方式影响CREB的磷酸化，在PKA-CREB信号通路中发挥作用。
