Shp2 suppresses PyMT-induced transformation in mouse fibroblasts by inhibiting Stat3 activity

Ying Yang, Beibei Jiang, Yingqing Huo, Luca Primo, Jean S. Dahl, Thomas L. Benjamin, Jincai Luo

Research output: Contribution to journalArticle

Abstract

We have examined the effect of expression of the protein tyrosine phosphatase Shp2 on transformation by the mouse polyoma virus middle T antigen (PyMT). Gain-of-function mutations in Shp2 indicate that it may serve as an oncogene in several types of human leukemia. Paradoxically, however, some catalytically dominant-negative mutations of Shp2 have also been identified in leukemia and neuroblastomas. In this study, we show that Shp2 suppresses transformation induced by PyMT, the major polyoma viral oncoprotein known to act through binding and activation of pp60c-src. Over-expression of a catalytically inactive Shp2 mutant in NIH3T3 cells significantly enhanced PyMT-induced transformation. Conversely, re-introduction of Shp2 into Shp2-deficient cells strongly inhibited PyMT-induced transformation and tumorigenesis. Short hairpin RNA (shRNA)-mediated Shp2 knockdown potentiated PyMT-induced transformation. Finally, we present evidence that the transformation-suppressive effects of Shp2 are mediated at least partially through the inhibition of signal transducers and activators of transcription 3.

Original languageEnglish
Pages (from-to)204-210
Number of pages7
JournalVirology
Volume409
Issue number2
DOIs
Publication statusPublished - Jan 20 2011

Keywords

  • Fibroblasts
  • Oncogene
  • Polyoma middle T antigen
  • Shp2
  • Signal transduction
  • Transformation

ASJC Scopus subject areas

  • Virology

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