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YAP and TAZ, Hippo signaling targets, act as a rheostat for nuclear SHP2 function

Ryouhei Tsutsumi1, Mohammad Masoudi, Atsushi Takahashi

  • 1Department of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Developmental Cell
|September 17, 2013
PubMed

Insights

The protein tyrosine phosphatase SHP2 interacts with YAP/TAZ, influencing their nuclear entry. Hippo signaling controls this interaction, regulating SHP2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • SHP2 (a protein tyrosine phosphatase) plays a role in RAS-Erk signaling and Wnt target gene activation.
  • SHP2 localization shifts between cytoplasm and nucleus based on cell density.
  • Deregulation of SHP2 is linked to cancers and developmental disorders.

Purpose of the Study:

  • To investigate the interaction between SHP2 and transcriptional coactivators YAP/TAZ.
  • To elucidate the role of the Hippo signaling pathway in regulating SHP2 nuclear localization.
  • To understand how cell density affects SHP2 function through YAP/TAZ.

Main Methods:

  • Co-immunoprecipitation to detect physical interactions between SHP2, YAP, and TAZ.
  • Western blotting to assess protein phosphorylation status.
  • Confocal microscopy to visualize subcellular localization of SHP2, YAP, and TAZ.

Main Results:

  • SHP2 physically interacts with YAP and TAZ.
  • Non-phosphorylated YAP/TAZ promote nuclear translocation of SHP2, enhancing TCF/LEF- and TEAD-regulated gene expression via parafibromin dephosphorylation.
  • Hippo-mediated phosphorylation of YAP/TAZ sequesters SHP2 in the cytoplasm, inhibiting its nuclear accumulation.

Conclusions:

  • YAP/TAZ act as a rheostat controlling nuclear SHP2 activity.
  • The Hippo signaling pathway regulates SHP2 function by modulating YAP/TAZ phosphorylation and subsequent SHP2 localization.
  • This mechanism links cell density sensing to the regulation of gene transcription mediated by SHP2, YAP, and TAZ.

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