Stimulation of an insulin receptor activates and down-regulates the Ca2+-independent protein kinase C, Apl II, through a Wortmannin-sensitive signaling pathway in Aplysia.
Activation of tyrosine kinase-linked receptors has been shown to stimulate Ca2+-independent protein kinase C isoforms in nonneuronal cells. We have examined this signaling pathway in the nervous system. Incubating bag cell neurons from the marine mollusk Aplysia californica with concentrations of insulin known to stimulate a tyrosine kinase-linked receptor in these cells persistently activated and down-regulated the Ca2+-independent protein kinase C (Apl II), whereas insulin only transiently activated and did not down-regulate the Ca2+-activated protein kinase C (Apl I). The effects of insulin may be mediated by activation of phosphoinositide 3-kinase because (a) diC16phosphatidylinositol 3,4,5-trisphosphate, a synthetic phosphoinositide 3-kinase product, stimulated autophosphorylation of baculovirus-expressed Apl II, but not of Apl I, and (b) wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked the activation and down-regulation of Apl II by insulin but not the transient activation of Apl I. These results suggest that activators of tyrosine kinase-linked receptors may mediate some of their effects in neurons through activation of Ca2+-independent protein kinase C isoforms.
Sossin
W S
WS
Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Chen
C S
CS
Toker
A
A
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000502:physiology*; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C; D002118:Calcium; D000077191:Wortmannin