Stimulation of neurite outgrowth in PC12 cells by EGF and KCl depolarization: a Ca(2+)-independent phenomenon.
MAP kinase activity is necessary for growth factor induction of neurite outgrowth in PC12 cells. Although NGF and EGF both stimulate MAP kinase activity, EGF does not stimulate neurite extension. We report that EGF, in combination with KCl, stimulates neurite outgrowth in PC12 cells. This phenomenon was independent of intracellular Ca2+ increases and not due to enhancement of MAP kinase activity over that seen with EGF alone. However, EGF plus KCl increased intracellular cAMP, and other cAMP elevating agents acted synergistically with EGF to promote neurite outgrowth. Stimulation of neurite outgrowth by cAMP and EGF was blocked by inhibitors of transcription suggesting that synergistic regulation of transcription by the cAMP and MAP kinase pathways may stimulate neurite growth.
Mark
M D
MD
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Liu
Y
Y
Wong
S T
ST
Hinds
T R
TR
Storm
D R
DR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic
D009414:Nerve Growth Factors; D004815:Epidermal Growth Factor; D011189:Potassium Chloride; D000242:Cyclic AMP; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium