Regulation of tyrosine phosphorylation and protein tyrosine phosphatases during oligodendrocyte differentiation.

Tyrosine phosphorylation is key to the differentiation of oligodendrocytes, as the FGF2 and PDGF receptor tyrosine kinases are known to mediate the proliferation and maintenance of their precursors. Marked changes in the levels and localization of tyrosine-phosphorylated proteins were found to accompany differentiation in the CG4 rat oligodendrocyte cell line. These alterations in phosphorylation as well as other differentiation-specific changes were found to be sensitive to inhibition by a tyrosine phosphatase inhibitor. This suggested that at some point early in the differentiation process, tyrosine phosphatases are important. A differential display strategy revealed 11 distinct tyrosine phosphatases in the oligodendrocyte lineage, with both precursor cells and oligodendrocytes expressing four major phosphatase transcripts: PTP alpha, PTP zeta, PTP sigma, and PTP gamma. A majority of the phosphatases examined show an increase in their mRNA levels during differentiation, with a striking upregulation observed for PTP epsilon. Our results suggest a significant role for this class of signal transducers in oligodendrocyte differentiation.