Regulation of localization and function of the transcriptional co-activator YAP by angiomotin

Elife. 2017 May 3;6:e23966. doi: 10.7554/eLife.23966.


The Hippo-YAP pathway is a central regulator of cell contact inhibition, proliferation and death. There are conflicting reports regarding the role of Angiomotin (Amot) in regulating this pathway. While some studies suggest a YAP-inhibitory function other studies indicate Amot is required for YAP activity. Here, we describe an Amot-dependent complex comprised of Amot, YAP and Merlin. The phosphorylation of Amot at Serine 176 shifts localization of this complex to the plasma membrane, where it associates with the tight-junction proteins Pals1/PATJ and E-cadherin. Conversely, hypophosphorylated Amot shifts localization of the complex to the nucleus, where it facilitates the association of YAP and TEAD, induces transcriptional activation of YAP target genes and promotes YAP-dependent cell proliferation. We propose that phosphorylation of AmotS176 is a critical post-translational modification that suppresses YAP's ability to promote cell proliferation and tumorigenesis by altering the subcellular localization of an essential YAP co-factor.

Keywords: Angiomotin; Hippo; YAP; cancer biology; cell biology; human; mouse.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Angiomotins
  • Cell Membrane / chemistry
  • Cell Nucleus / chemistry
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Microfilament Proteins
  • Neurofibromin 2 / metabolism*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Multimerization*
  • Protein Processing, Post-Translational*
  • Transcription Factors
  • YAP-Signaling Proteins


  • AMOT protein, human
  • Adaptor Proteins, Signal Transducing
  • Angiomotins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Neurofibromin 2
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human