MAP kinase phosphatase-1 mRNA is expressed in embryonic sympathetic neurons and is upregulated after NGF stimulation.
The family of Tyr/Thr protein phosphatases, called dual-specificity phosphatases, have been implicated in the feedback regulation of the MAP kinase cascade by dephosphorylating the MAP kinases. Using low stringent cDNA screening we have isolated a chicken homologue of the CL100 phosphatase also called MAP kinase phosphatase 1 (MKP-1). The chicken MKP-1 has 84% and 85.5% identity to the rat and human amino acid sequence, respectively. Using RNase protection assay and in situ hybridization we have found that MKP-1 mRNA is expressed at low levels in most tissues during development. In embryonic dorsal root and sympathetic ganglia MKP-1 mRNA expression increases with age. The expression in large cells in dorsal root ganglia suggests that it is neurons which express MKP-1 mRNA. We also show that MKP-1 mRNA is induced in dissociated embryonic sympathetic neurons after nerve growth factor stimulation. In addition, our results show that MKP-1 mRNA is induced after NGF stimulation of fibroblasts expressing the NGF receptor TrkA, suggesting that MKP-1 is upregulated after activation of the TrkA receptor. These data show that the MKP-1 gene is regulated in a tissue and temporal specific fashion with strong expression in the developing peripheral ganglia, and suggest that the activation of MKP-1 mRNA expression by NGF is a ubiquitously induced response to TrkA activation, independent of the cellular origin or type on which the TrkA receptor is active.
Peinado-Ramón
P
P
Department of Developmental Neuroscience, Biomedical Centre, University of Uppsala, Box 587, S-751 23, Uppsala, Sweden.
Wallén
A
A
Hallböök
F
F
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology; D018797:Cell Cycle Proteins; D002642:Chick Embryo; D002645:Chickens; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D054638:Dual Specificity Phosphatase 1; D005728:Ganglia, Sympathetic / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases