Tyrosine phosphorylation of myelin P0 and its implication in signal transduction

Ming Jiang Xu, Runxiang Zhao, Xingwei Sui, Fengping Xu, Zhizhuang Joe Zhao

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

P0 a major structural protein of peripheral myelin, belongs to the immunoglobulin superfamily. Sequence comparison of P0 with PZR, a tyrosine phosphatase SHP-2 binding protein we recently cloned, revealed the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the intracellular portion of the P0 molecule. To study the role of this putative ITIM in signal transduction, we have expressed P0 in HT-1080 and 293 cells. Stimulation of the transfected cells with pervanadate, a powerful inhibitor of tyrosine phosphatases, resulted in tyrosine phosphorylation of P0 and its association with several tyrosine-phosphorylated proteins. Mutation of Y220 embedded in the ITIM to phenylalanine abolished the tyrosine phosphorylation and the association. Tyrosine phosphorylation of P0 and its association with other signaling proteins were also observed in pervanadate-treated RN22 Schwannoma cells, which express endogenous P0. Furthermore, injection of pervanadate induced tyrosine phosphorylation of P0 in peripheral nerves of newborn but not adult mice. The physiological importance of the ITIM in P0 is implied by the fact that a naturally occurred P0 mutant with a disrupted ITIM has a dominant role in causing Dejerine-Scotts syndrome. Taken together, P0 is phosphorylated on Try220. The presence of an ITIM in P0 and its ability to mediate protein-protein interaction through tyrosine phosphorylation indicate that P0 is not merely a structural protein but may also be a crucial player in cell signaling. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)820-825
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume267
Issue number3
DOIs
StatePublished - Jan 27 2000

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Keywords

  • ITIM
  • Myelin P
  • Pervanadate
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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