scholarly journals Bioinformatics Approaches for Predicting Kinase–Substrate Relationships

Author(s):  
Daniel A. Bórquez ◽  
Christian González-Billault
Keyword(s):  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aijun Qiao ◽  
Junlan Zhou ◽  
Shiyue Xu ◽  
Wenxia Ma ◽  
Chan Boriboun ◽  
...  

AbstractHepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68ΔC) or N-terminal (Sam68ΔN) domains fails to bind CRTC2 or to stabilize CRTC2 protein, respectively, and transgenic Sam68ΔN mice recapitulate the blood-glucose and gluconeogenesis profile of Sam68-deficient mice. Hepatic Sam68 expression is also upregulated in patients with diabetes and in two diabetic mouse models, while hepatocyte-specific Sam68 deficiencies alleviate diabetic hyperglycemia and improves insulin sensitivity in mice. Thus, our results identify a role for Sam68 in hepatic gluconeogenesis, and Sam68 may represent a therapeutic target for diabetes.


Author(s):  
Aparna Krishnan ◽  
Kristin Leskoske ◽  
Krystine Garcia-Mansfield ◽  
Ritin Sharma ◽  
Jessica Rusert ◽  
...  

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