In fasting mammals,the liver is the primary source of glucose production for maintenance of normoglycemia.In this setting,circulating peptide hormones and catecholamines cause hepatic glucose output by stimulating gly...In fasting mammals,the liver is the primary source of glucose production for maintenance of normoglycemia.In this setting,circulating peptide hormones and catecholamines cause hepatic glucose output by stimulating glycogen breakdown as well as de novo glucose production through gluconeogenesis.Fasting gluconeogenesis is regulated by a complex transcriptional cascade culminating in elevated expression of hepatic enzymes that promote gluconeogenesis and glucose export to the blood.The cAMP response element binding protein CREB and its co-activator CRTC2 play crucial roles in signal-dependent transcriptional regulation of gluconeogenesis.Recent work has identified a family of serine/threonine kinases,the salt inducible kinases(SIKs),which are subject to hormonal control and constrain gluconeogenic and lipogenic gene expression in liver.As normal regulation of gluconeogenesis and lipogenesis is disrupted in diabetic states,SIK kinases are poised to serve as therapeutic targets to modulate metabolic disturbances in diabetic patients.The purpose of this review is to 1)describe the identification of CRTCs CREB co-activators and their regulation by SIKs,2)discuss recent progress toward understanding regulation and function of SIKs in metabolism and 3)examine the potential clinical impact of therapeutics that target SIK kinase function.展开更多
盐诱导激酶(salt-inducible kinase,SIK)是属于单磷酸腺苷激活蛋白激酶/蔗糖非酵解1(adenosine monophosphate-activated protein kinase and sucrose non-fermenting 1,AMPK/SNF1)家族的丝氨酸/苏氨酸蛋白激酶。SIK自1998年被发现以来...盐诱导激酶(salt-inducible kinase,SIK)是属于单磷酸腺苷激活蛋白激酶/蔗糖非酵解1(adenosine monophosphate-activated protein kinase and sucrose non-fermenting 1,AMPK/SNF1)家族的丝氨酸/苏氨酸蛋白激酶。SIK自1998年被发现以来,越来越多的功能被人们证实和认可。现已发现,SIK在能量代谢、细胞信号转导、细胞周期、肿瘤、黑素原生成等诸多方面有重要作用。通过查阅近些年相关文献,在此重点总结一下SIK2功能的研究进展。展开更多
基金supported by grants from the Muscular Dystrophy Association(MDA 68640)the American Heart Association(AHA 09BGIA2261362)the University of Texas Health Science Center,Houston.
文摘In fasting mammals,the liver is the primary source of glucose production for maintenance of normoglycemia.In this setting,circulating peptide hormones and catecholamines cause hepatic glucose output by stimulating glycogen breakdown as well as de novo glucose production through gluconeogenesis.Fasting gluconeogenesis is regulated by a complex transcriptional cascade culminating in elevated expression of hepatic enzymes that promote gluconeogenesis and glucose export to the blood.The cAMP response element binding protein CREB and its co-activator CRTC2 play crucial roles in signal-dependent transcriptional regulation of gluconeogenesis.Recent work has identified a family of serine/threonine kinases,the salt inducible kinases(SIKs),which are subject to hormonal control and constrain gluconeogenic and lipogenic gene expression in liver.As normal regulation of gluconeogenesis and lipogenesis is disrupted in diabetic states,SIK kinases are poised to serve as therapeutic targets to modulate metabolic disturbances in diabetic patients.The purpose of this review is to 1)describe the identification of CRTCs CREB co-activators and their regulation by SIKs,2)discuss recent progress toward understanding regulation and function of SIKs in metabolism and 3)examine the potential clinical impact of therapeutics that target SIK kinase function.
文摘盐诱导激酶(salt-inducible kinase,SIK)是属于单磷酸腺苷激活蛋白激酶/蔗糖非酵解1(adenosine monophosphate-activated protein kinase and sucrose non-fermenting 1,AMPK/SNF1)家族的丝氨酸/苏氨酸蛋白激酶。SIK自1998年被发现以来,越来越多的功能被人们证实和认可。现已发现,SIK在能量代谢、细胞信号转导、细胞周期、肿瘤、黑素原生成等诸多方面有重要作用。通过查阅近些年相关文献,在此重点总结一下SIK2功能的研究进展。
