Does mitogen-activated-protein kinase have a role in insulin action? The cases for and against.
The discovery of the mitogen-activated protein (MAP) kinase family of protein kinases has sparked off an intensive effort to elucidate their role in the regulation of many cellular processes. These protein kinases were originally identified based on their rapid activation by insulin. In this review we concentrate on examining the evidence for and against a role for the MAP kinases Erk-1 and Erk-2 in mediating the effects of insulin. While there is good evidence in favour of a direct role for MAP kinase in the growth-promoting effects of insulin and the regulation of Glut-1 and c-fos expression, and AP-1 transcriptional complex activity, this is by no means conclusive. MAP kinase may also play a role in the control of mRNA translation by insulin. On the other hand, the evidence suggests that MAP kinase is not sufficient for the acute regulation of glucose transport (Glut-4 translocation), glycogen synthesis, acetyl-CoA carboxylase or pyruvate dehydrogenase activity. The findings suggest that insulin may utilise at least three distinct signalling pathways which do not involve MAP kinase.
Denton
R M
RM
Department of Biochemistry, School of Medical Sciences, University of Bristol, England.
Tavaré
J M
JM
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis; D005821:Genetic Techniques; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008954:Models, Biological; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014158:Transcription, Genetic
D005227:Fatty Acids; D007328:Insulin; D012333:RNA, Messenger; D006006:Glycogen Synthase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005947:Glucose