MAP KINASE PHOSPHATASE-1 MESSENGER-RNA IS EXPRESSED IN EMBRYONIC SYMPATHETIC NEURONS AND IS UP-REGULATED AFTER NGF STIMULATION

The family of Tyr/Thr protein phosphatases, called dual-specificity ph osphatases, have been implicated in the feedback regulation of the MAP kinase cascade by dephosphorylating the MAP kinases. Using low string ent cDNA screening we have isolated a chicken homologue of the CL100 p hosphatase also called MAP kinase phosphatase 1 (MKP-1). The chicken M KP-1 has 84% and 85.5% identity to the rat and human amino acid sequen ce, respectively. Using RNase protection assay and in situ hybridizati on we have found that MKP-1 mRNA is expressed at low levels in most ti ssues during development. In embryonic dorsal root and sympathetic gan glia MKP-1 mRNA expression increases with age. The expression in large cells in dorsal root ganglia suggests that it is neurons which expres s MKP-1 mRNA. We also show that MKP-1 mRNA is induced in dissociated e mbryonic sympathetic neurons after nerve growth factor stimulation. In addition, our results show that MKP-1 mRNA is induced after NGF stimu lation of fibroblasts expressing the NGF receptor TrkA, suggesting tha t MKP-1 is upregulated after activation of the TrkA receptor. These da ta show that the MKP-1 gene is regulated in a tissue and temporal spec ific fashion with strong expression in the developing peripheral gangl ia, and suggest that the activation of MKP-1 mRNA expression by NGF is a ubiquitously induced response to TrkA activation, independent of th e cellular origin or type on which the TrkA receptor is active. (C) 19 98 Elsevier Science B.V.