Insulin-induced expression of the activity-regulated cytoskeleton-associated gene (ARC) in human neuroblastoma cells requires p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and src tyrosine kinases but is protein kinase C-independent.
We examined the effect of insulin on the expression of the activity-regulated cytoskeleton-associated gene (ARC), an effector immediate early gene with a proposed role in memory formation. In human SH-SY5Y neuroblastoma cells, application of insulin leads to dramatic increase in ARC mRNA and protein levels. Inhibition experiments reveal, that p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and tyrosine kinase (src) activity are required for the insulin-induced ARC expression in SH-SY5Y cells, whereas protein kinase C is not involved in the signal transduction pathway. Our data indicated for the first time a correlation of the insulin-controlled signal cascade and the induction of synaptic plasticity-associated immediate early genes.
Kremerskothen
Joachim
J
Department for Experimental Tumor Biology, University Muenster, Badestrasse 9, 48149 Muenster, Germany. kremers@uni-muenster.de
Wendholt
Doreen
D
Teber
Iskender
I
Barnekow
Angelika
A
D002490:Central Nervous System / Q000201:enzymology / Q000254:growth & development; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008568:Memory / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D007328:Insulin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D019061:src-Family Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)