Abstract
The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here, we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension. We show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens junctions and stimulating its binding to and inhibition of LATS1/2 in response to tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1 from recruiting the LATS1/2 activating kinases MST1/2. Together, these findings reveal a novel pathway that responds to tension at adherens junctions to control Hippo pathway signaling.
Keywords:
TRIP6; Vinculin; YAP; adherens junctions; mechano‐sensing.
© 2017 The Authors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Adherens Junctions / metabolism*
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Biomarkers
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Cell Line
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Gene Expression
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Hippo Signaling Pathway
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Humans
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LIM Domain Proteins / genetics
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LIM Domain Proteins / metabolism*
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Phosphoproteins / metabolism
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Protein Binding
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Protein Serine-Threonine Kinases / metabolism*
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Protein Transport
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RNA, Small Interfering / genetics
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Recombinant Fusion Proteins
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Signal Transduction*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Suppressor Proteins / metabolism
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Biomarkers
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LIM Domain Proteins
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Phosphoproteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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TRIP6 protein, human
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Transcription Factors
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Tumor Suppressor Proteins
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YAP-Signaling Proteins
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YAP1 protein, human
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LATS1 protein, human
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LATS2 protein, human
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Protein Serine-Threonine Kinases