PMID- 20498073
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 23
DP  - 2010 Jun 8
TI  - The apical transmembrane protein Crumbs functions as a tumor suppressor that 
      regulates Hippo signaling by binding to Expanded.
PG  - 10532-7
LID - 10.1073/pnas.1004279107 [doi]
AB  - The Hippo signaling pathway regulates organ size and tissue homeostasis from 
      Drosophila to mammals. At the core of the Hippo pathway is a kinase cascade 
      extending from the Hippo (Hpo) tumor suppressor to the Yorkie (Yki) oncoprotein. 
      The Hippo kinase cascade, in turn, is regulated by apical membrane-associated 
      proteins such as the FERM domain proteins Merlin and Expanded (Ex), and the WW- 
      and C2-domain protein Kibra. How these apical proteins are themselves regulated 
      remains poorly understood. Here, we identify the transmembrane protein Crumbs 
      (Crb), a determinant of epithelial apical-basal polarity in Drosophila embryos, 
      as an upstream component of the Hippo pathway in imaginal disk growth control. 
      Loss of Crb leads to tissue overgrowth and target gene expression characteristic 
      of defective Hippo signaling. Crb directly binds to Ex through its juxtamembrane 
      FERM-binding motif (FBM). Loss of Crb or mutation of its FBM leads to 
      mislocalization of Ex to basolateral domain of imaginal disk epithelial cells. 
      These results shed light on the mechanism of Ex regulation and provide a 
      molecular link between apical-basal polarity and tissue growth. Furthermore, our 
      studies implicate Crb as a putative cell surface receptor for Hippo signaling by 
      uncovering a transmembrane protein that directly binds to an apical component of 
      the Hippo pathway.
FAU - Ling, Chen
AU  - Ling C
AD  - Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, 
      Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
FAU - Zheng, Yonggang
AU  - Zheng Y
FAU - Yin, Feng
AU  - Yin F
FAU - Yu, Jianzhong
AU  - Yu J
FAU - Huang, Juan
AU  - Huang J
FAU - Hong, Yang
AU  - Hong Y
FAU - Wu, Shian
AU  - Wu S
FAU - Pan, Duojia
AU  - Pan D
LA  - eng
GR  - R01 EY015708/EY/NEI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - EY015708/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100524
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Drosophila Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (crb protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Cell Polarity
MH  - Conserved Sequence
MH  - Drosophila Proteins/chemistry/genetics/*metabolism
MH  - Drosophila melanogaster/cytology/*embryology/growth & development/*metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Membrane Proteins/chemistry/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - *Signal Transduction
MH  - Tumor Suppressor Proteins/chemistry/genetics/*metabolism
PMC - PMC2890787
COIS- The authors declare no conflict of interest.
EDAT- 2010/05/26 06:00
MHDA- 2010/07/20 06:00
PMCR- 2010/12/08
CRDT- 2010/05/26 06:00
PHST- 2010/05/26 06:00 [entrez]
PHST- 2010/05/26 06:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
PHST- 2010/12/08 00:00 [pmc-release]
AID - 1004279107 [pii]
AID - 201004279 [pii]
AID - 10.1073/pnas.1004279107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10532-7. doi: 
      10.1073/pnas.1004279107. Epub 2010 May 24.