Rapid deactivation of MAP kinase in PC12 cells occurs independently of induction of phosphatase MKP-1.
Growth factors or serum can induce transcription and translation of a dual specificity MAP (mitogen-activated protein) kinase phosphatase, MKP-1 (MAP kinase phosphatase-1). The role of induction of MKP-1 (formerly 3CH134) in the rapid phase of MAP kinase deactivation was studied in rat pheochromocytoma (PC12) cells. MAP kinase was nearly completely deactivated in PC12 cells by 10 min after stimulation with epidermal growth factor (EGF) whereas MAP kinase activity remained elevated at 30% of the maximal response after stimulation with nerve growth factor. Protocols for treating cells with actinomycin D and cycloheximide were established that eliminate detection of MKP-1 mRNA and protein in PC 12 cells. Treatment of PC12 cells with actinomycin D and cycloheximide did not affect the rapid deactivation of MAP kinase. Thus, the rapid phase of MAP kinase deactivation in PC12 cells is not dependent on the induction of the MAP kinase phosphatase MKP-1.
Wu
J
J
Department of Medicine, Howard Hughes Medical Institute, University of Virginia Health Sciences Center, Charlottesville 22908.
Lau
L F
LF
Sturgill
T W
TW
D016475:3T3 Cells; D000818:Animals; D018797:Cell Cycle Proteins; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D054638:Dual Specificity Phosphatase 1; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases