Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes.
Previous studies in this laboratory have shown that the SH-2 domain-containing protein tyrosine phosphatase SHP-1 is expressed in CNS glia and functions to modulate cytokine activities in these cells. The present study demonstrates that SHP-1 is expressed within multiple regions of the CNS in vivo, especially in white matter. Interestingly, we show that mice genetically lacking in SHP-1 (motheaten mice) in the CNS displayed dysmyelination. We therefore examined the expression of SHP-1 in the myelin-forming oligodendrocytes. Oligodendrocytes present in either mixed glial cultures or pure cultures expressed high levels of SHP-1 in the cytoplasm of cell bodies and processes. Oligodendrocytes isolated from motheaten mice did not express SHP-1. To test possible functions for SHP-1 in oligodendrocytes in controlling cytokine signaling, we compared the responsiveness of oligodendrocytes isolated from either motheaten or normal littermate mice with IL-6. IL-6 induced higher levels of STAT3 phosphorylation and STAT3-responsive c-fos gene expression in pure oligodendrocyte cultures of motheaten compared with normal littermate mice. These studies demonstrate that oligodendrocytes express SHP-1 and that SHP-1 functions to control IL-6 signaling. SHP-1 may therefore be a critical regulator of oligodendrocyte differentiation in response to IL-6 family cytokines. Further, these findings may relate to dysmyelination in mice lacking SHP-1.
Massa
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PT
Departments of Neurology, State University of New York Health Science Center, Syracuse, New York 13210, USA. massap@hscsyr.edu
Saha
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Wu
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Jarosinski
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction; D016762:Genes, fos; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009836:Oligodendroglia / Q000201:enzymology* / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D003165:Complement System Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse