| First Author | Kumar A | Year | 2023 |
| Journal | J Biol Chem | Volume | 299 |
| Issue | 9 | Pages | 105164 |
| PubMed ID | 37595871 | Mgi Jnum | J:340798 |
| Mgi Id | MGI:7530254 | Doi | 10.1016/j.jbc.2023.105164 |
| Citation | Kumar A, et al. (2023) SHP-1 phosphatase acts as a coactivator of PCK1 transcription to control gluconeogenesis. J Biol Chem 299(9):105164 |
| abstractText | We previously reported that the protein-tyrosine phosphatase SHP-1 (PTPN6) negatively regulates insulin signaling, but its impact on hepatic glucose metabolism and systemic glucose control remains poorly understood. Here, we use co-immunoprecipitation assays, chromatin immunoprecipitation sequencing, in silico methods, and gluconeogenesis assay, and found a new mechanism whereby SHP-1 acts as a coactivator for transcription of the phosphoenolpyruvate carboxykinase 1 (PCK1) gene to increase liver gluconeogenesis. SHP-1 is recruited to the regulatory regions of the PCK1 gene and interacts with RNA polymerase II. The recruitment of SHP-1 to chromatin is dependent on its association with the transcription factor signal transducer and activator of transcription 5 (STAT5). Loss of SHP-1 as well as STAT5 decrease RNA polymerase II recruitment to the PCK1 promoter and consequently PCK1 mRNA levels leading to blunted gluconeogenesis. This work highlights a novel nuclear role of SHP-1 as a key transcriptional regulator of hepatic gluconeogenesis adding a new mechanism to the repertoire of SHP-1 functions in metabolic control. |
