PMID- 26109051
OWN - NLM
STAT- MEDLINE
DCOM- 20150903
LR  - 20211203
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 29
IP  - 12
DP  - 2015 Jun 15
TI  - Homeostatic control of Hippo signaling activity revealed by an endogenous 
      activating mutation in YAP.
PG  - 1285-97
LID - 10.1101/gad.264234.115 [doi]
AB  - The Hippo signaling pathway converges on YAP to regulate growth, differentiation, 
      and regeneration. Previous studies with overexpressed proteins have shown that 
      YAP is phosphorylated by its upstream kinase, Lats1/2, on multiple sites, 
      including an evolutionarily conserved 14-3-3-binding site whose phosphorylation 
      is believed to inhibit YAP by excluding it from the nucleus. Indeed, nuclear 
      localization of YAP or decreased YAP phosphorylation at this site (S168 in 
      Drosophila, S127 in humans, and S112 in mice) is widely used in current 
      literature as a surrogate of YAP activation even though the physiological 
      importance of this phosphorylation event in regulating endogenous YAP activity 
      has not been defined. Here we address this question by introducing a Yap(S112A) 
      knock-in mutation in the endogenous Yap locus. The Yap(S112A) mice are 
      surprisingly normal despite nuclear localization of the mutant YAP protein in 
      vivo and profound defects in cytoplasmic translocation in vitro. Interestingly, 
      the mutant Yap(S112A) mice show a compensatory decrease in YAP protein levels due 
      to increased phosphorylation at a mammalian-specific phosphodegron site on YAP. 
      These findings reveal a robust homeostatic mechanism that maintains physiological 
      levels of YAP activity and caution against the assumptive use of YAP localization 
      alone as a surrogate of YAP activity.
CI  - (c) 2015 Chen et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Chen, Qian
AU  - Chen Q
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Zhang, Nailing
AU  - Zhang N
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Xie, Rui
AU  - Xie R
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Wang, Wei
AU  - Wang W
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Cai, Jing
AU  - Cai J
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Choi, Kyung-Suk
AU  - Choi KS
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - David, Karen Kate
AU  - David KK
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Huang, Bo
AU  - Huang B
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
FAU - Yabuta, Norikazu
AU  - Yabuta N
AD  - Department of Molecular Genetics, Osaka University, Suita City, Osaka 565-0871, 
      Japan;
FAU - Nojima, Hiroshi
AU  - Nojima H
AD  - Department of Molecular Genetics, Osaka University, Suita City, Osaka 565-0871, 
      Japan;
FAU - Anders, Robert A
AU  - Anders RA
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland 21205, USA.
FAU - Pan, Duojia
AU  - Pan D
AD  - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, 
      Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
LA  - eng
GR  - R01 EY015708/EY/NEI NIH HHS/United States
GR  - EY015708/EY/NEI NIH HHS/United States
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics/*metabolism
MH  - Animals
MH  - Cell Cycle Proteins
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Cytoplasm/metabolism
MH  - Feedback, Physiological
MH  - Gene Expression Regulation, Developmental
MH  - Gene Knock-In Techniques
MH  - Hippo Signaling Pathway
MH  - Homeostasis/genetics/*physiology
MH  - Liver/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation
MH  - Phosphoproteins/*genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/*physiology
MH  - Protein Transport/genetics
MH  - Signal Transduction/*physiology
MH  - YAP-Signaling Proteins
PMC - PMC4495399
OTO - NOTNLM
OT  - 14-3-3
OT  - Hippo signaling
OT  - YAP oncoprotein
OT  - phosphorylation
OT  - tumorigenesis
EDAT- 2015/06/26 06:00
MHDA- 2015/09/04 06:00
PMCR- 2015/12/15
CRDT- 2015/06/26 06:00
PHST- 2015/06/26 06:00 [entrez]
PHST- 2015/06/26 06:00 [pubmed]
PHST- 2015/09/04 06:00 [medline]
PHST- 2015/12/15 00:00 [pmc-release]
AID - 29/12/1285 [pii]
AID - 10.1101/gad.264234.115 [doi]
PST - ppublish
SO  - Genes Dev. 2015 Jun 15;29(12):1285-97. doi: 10.1101/gad.264234.115.