REGULATION OF TYROSINE PHOSPHORYLATION AND PROTEIN-TYROSINE PHOSPHATASES DURING OLIGODENDROCYTE DIFFERENTIATION

Tyrosine phosphorylation is key to the differentiation of oligodendroc ytes, as the FGF2 and PDGF receptor tyrosine kinases are known to medi ate the proliferation and maintenance of their precursors. Marked chan ges in the levels and localization of tyrosine-phosphorylated proteins were found to accompany differentiation in the CG4 rat oligodendrocyt e cell line. These alterations in phosphorylation as well as other dif ferentiation-specific changes were found to be sensitive to inhibition by a tyrosine phosphatase inhibitor. This suggested that at some poin t early in the differentiation process, tyrosine phosphatases are impo rtant. A differential display strategy revealed 11 distinct tyrosine p hosphatases in the oligodendrocyte lineage, with both precursor cells and oligodendrocytes expressing four major phosphatase transcripts: PT P alpha, PTP zeta, PTP sigma, and PTP gamma. A majority of the phospha tases examined show an increase in their mRNA levels during differenti ation, with a striking upregulation observed for PTP epsilon. Our resu lts suggest a significant role for this class of signal transducers in oligodendrocyte differentiation.