Insulin and IGF-I receptor signaling in cultured neurons.
The data presented in this chapter are summarized in the schematic shown in Figure 9. Insulin binds to and stimulates autophosphorylation of neuronal insulin receptors, whereas, IGF-I and IGF-II binds to and stimulate autophosphorylation of neuronal IGF-I receptors. IGF-II is also capable of binding to the insulin receptor. Whether or not it activates the insulin receptor kinase remains to be clarified. Activated insulin and IGF-I receptor kinases phosphorylate a 70-kDa protein at early times in culture. This protein may mediate some actions of insulin, but we speculate that there are other intermediary proteins involved in the transduction pathway resulting in the activation of S6 kinase and PKC epsilon. The stimulation of S6 kinase by insulin and IGF-I may be associated with the translational activation of protein synthesis by these peptides. The stimulation of PKC epsilon appears to be a necessary step in the transcriptional regulation of the c-fos gene by insulin and IGF-I. The regulation of neuronal protein synthesis at a translational step and the initiation of transcriptional programs regulated by AP-1 represent two mechanisms by which insulin and IGFs alter neuronal growth and differentiation.
Heidenreich
K A
KA
Department of Pharmacology C-236, University of Colorado Health Science Center, Denver.
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D016762:Genes, fos / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D011972:Receptor, Insulin / Q000502:physiology*; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D011493:Protein Kinase C