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O-GlcNAcylation modulates PKA-CREB signaling in a manner specific to PKA catalytic subunit isoforms
Nana Jin1, Denglei Ma2, Jianlan Gu1
1Key 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.
Abstract:
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.
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