Differentiation of PC12 cells in response to a cAMP analogue is accompanied by sustained activation of mitogen-activated protein kinase. Comparison with the effects of insulin, growth factors and phorbol esters.
It has been proposed previously that the sustained activation of mitogen-activated protein kinase may be necessary for the differentiation of PC12 cells. Differentiation of PC12 cells is induced by many extracellular agonists including nerve growth factor (NGF) and cyclicAMP analogues, but not epidermal growth factor (EGF), insulin or phorbol esters. Our results demonstrate that: (i) 8-(4-chlorophenylthio)-cyclicAMP (CPT-cAMP) activates MAP kinase; this raises the possibility that the MAP kinase pathway may be activated by agents that act through adenylate cyclase; (ii) NGF and CPT-cAMP as well as phorbol esters promote sustained activation of MAP kinase. This suggests that while sustained MAP kinase activation may be associated with differentiation it may not be sufficient, and that other as yet unidentified parallel pathways may be involved.
Young
S W
SW
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Dickens
M
M
Tavaré
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D016716:PC12 Cells / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*
D006133:Growth Substances; D007328:Insulin; D009414:Nerve Growth Factors; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate