SH2-containing phosphotyrosine phosphatase Syp is a target of p210bcr-abl tyrosine kinase

Tetsuzo Tauchi, Gen Sheng Feng, Randy Shen, Ho Yeong Song, David Donner, Tony Pawson, Hal E. Broxmeyer

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Abstract

The phosphorylation of proteins at tyrosine residues is critical in cellular signal transduction and neoplastic transformation. These mechanisms are regulated by the activities of both protein-tyrosine kinases and protein- tyrosine phosphatases. Recent studies have identified a novel protein- tyrosine phosphatase, termed Syp, that is widely expressed in various tissues. Syp encodes a cytoplasmic phosphatase that contains two Src homology 2 (SH2) domains. Since SH2 domains have been shown to target the association of signal-transducing molecules to activated tyrosine kinases, experiments were performed to determine whether Syp might form specific complexes with p210bcr-abl, a fusion protein believed to be involved in the pathogenesis of chronic myelogenous leukemia and, thus, possibly alter or mediate p210bcr- abl tyrosine kinase activity. We found that Syp was highly and constitutively tyrosine phosphorylated in three different murine cell lines transfected with a p210bcr-abl expression vector. Furthermore, p210bcr-abl, Syp, and Grb2 formed stable complexes in BCR-ABL-expressing cells. Complex formation between p210bcr-abl and Syp was mediated in vitro by the NH2-terminal SH2 domain of Syp. Last, p210bcr-abl tyrosine kinase was effectively dephosphorylated by Syp in vitro. These results suggest an interaction between Syp and BCR-ABL protein, which might play a role in cellular transformation of BCR-ABL.

Original languageEnglish (US)
Pages (from-to)15381-15387
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number21
StatePublished - May 27 1994

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tauchi, T., Feng, G. S., Shen, R., Song, H. Y., Donner, D., Pawson, T., & Broxmeyer, H. E. (1994). SH2-containing phosphotyrosine phosphatase Syp is a target of p210bcr-abl tyrosine kinase. Journal of Biological Chemistry, 269(21), 15381-15387.