PMID- 25453828
OWN - NLM
STAT- MEDLINE
DCOM- 20150311
LR  - 20211203
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 31
IP  - 3
DP  - 2014 Nov 10
TI  - The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate 
      intestinal stem cells in Drosophila.
PG  - 291-304
LID - S1534-5807(14)00618-2 [pii]
LID - 10.1016/j.devcel.2014.09.012 [doi]
AB  - Similar to the mammalian intestine, the Drosophila adult midgut has resident stem 
      cells that support growth and regeneration. How the niche regulates intestinal 
      stem cell activity in both mammals and flies is not well understood. Here, we 
      show that the conserved germinal center protein kinase Misshapen restricts 
      intestinal stem cell division by repressing the expression of the JAK-STAT 
      pathway ligand Upd3 in differentiating enteroblasts. Misshapen, a distant 
      relative to the prototypic Warts activating kinase Hippo, interacts with and 
      activates Warts to negatively regulate the activity of Yorkie and the expression 
      of Upd3. The mammalian Misshapen homolog MAP4K4 similarly interacts with LATS 
      (Warts homolog) and promotes inhibition of YAP (Yorkie homolog). Together, this 
      work reveals that the Misshapen-Warts-Yorkie pathway acts in enteroblasts to 
      control niche signaling to intestinal stem cells. These findings also provide a 
      model in which to study requirements for MAP4K4-related kinases in 
      MST1/2-independent regulation of LATS and YAP.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Li, Qi
AU  - Li Q
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Li, Shuangxi
AU  - Li S
AD  - Department of Developmental Biology, University of Texas Southwestern Medical 
      Center, Dallas, TX 75390, USA.
FAU - Mana-Capelli, Sebastian
AU  - Mana-Capelli S
AD  - Department of Biochemistry and Molecular Pharmacology, University of 
      Massachusetts Medical School, Worcester, MA 01605, USA.
FAU - Roth Flach, Rachel J
AU  - Roth Flach RJ
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Danai, Laura V
AU  - Danai LV
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Amcheslavsky, Alla
AU  - Amcheslavsky A
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Nie, Yingchao
AU  - Nie Y
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Kaneko, Satoshi
AU  - Kaneko S
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Yao, Xiaohao
AU  - Yao X
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Chen, Xiaochu
AU  - Chen X
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Cotton, Jennifer L
AU  - Cotton JL
AD  - Department of Cancer Biology, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Mao, Junhao
AU  - Mao J
AD  - Department of Cancer Biology, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - McCollum, Dannel
AU  - McCollum D
AD  - Department of Biochemistry and Molecular Pharmacology, University of 
      Massachusetts Medical School, Worcester, MA 01605, USA.
FAU - Jiang, Jin
AU  - Jiang J
AD  - Department of Developmental Biology, University of Texas Southwestern Medical 
      Center, Dallas, TX 75390, USA.
FAU - Czech, Michael P
AU  - Czech MP
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA.
FAU - Xu, Lan
AU  - Xu L
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA. Electronic address: lxu@blueprintmedicines.com.
FAU - Ip, Y Tony
AU  - Ip YT
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA 01605, USA. Electronic address: tony.ip@umassmed.edu.
LA  - eng
GR  - R01 GM067045/GM/NIGMS NIH HHS/United States
GR  - R01 GM058406/GM/NIGMS NIH HHS/United States
GR  - UL1TR000161/TR/NCATS NIH HHS/United States
GR  - R01 GM106188/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000161/TR/NCATS NIH HHS/United States
GR  - P30 DK032520/DK/NIDDK NIH HHS/United States
GR  - DK32520/DK/NIDDK NIH HHS/United States
GR  - GM67045/GM/NIGMS NIH HHS/United States
GR  - R01 DK083450/DK/NIDDK NIH HHS/United States
GR  - DK030898/DK/NIDDK NIH HHS/United States
GR  - R37 DK030898/DK/NIDDK NIH HHS/United States
GR  - GM61269/GM/NIGMS NIH HHS/United States
GR  - R01 GM061269/GM/NIGMS NIH HHS/United States
GR  - DK83450/DK/NIDDK NIH HHS/United States
GR  - R01 DK030898/DK/NIDDK NIH HHS/United States
GR  - GM058406-14/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141110
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (Drosophila Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yki protein, Drosophila)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (msn protein, Drosophila)
RN  - EC 2.7.1.- (wts protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Cell Division
MH  - Drosophila Proteins/*metabolism
MH  - Drosophila melanogaster/*metabolism
MH  - Intestinal Mucosa/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Regeneration/genetics/*physiology
MH  - Signal Transduction/*physiology
MH  - Stem Cells/cytology
MH  - Trans-Activators/*metabolism
MH  - YAP-Signaling Proteins
PMC - PMC4254555
MID - NIHMS632786
EDAT- 2014/12/03 06:00
MHDA- 2015/03/12 06:00
PMCR- 2015/11/10
CRDT- 2014/12/03 06:00
PHST- 2014/04/01 00:00 [received]
PHST- 2014/08/14 00:00 [revised]
PHST- 2014/09/23 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/03/12 06:00 [medline]
PHST- 2015/11/10 00:00 [pmc-release]
AID - S1534-5807(14)00618-2 [pii]
AID - 10.1016/j.devcel.2014.09.012 [doi]
PST - ppublish
SO  - Dev Cell. 2014 Nov 10;31(3):291-304. doi: 10.1016/j.devcel.2014.09.012. Epub 2014 
      Nov 10.