PMID- 24255178
OWN - NLM
STAT- MEDLINE
DCOM- 20140802
LR  - 20220309
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 6
IP  - 302
DP  - 2013 Nov 19
TI  - Protein interaction network of the mammalian Hippo pathway reveals mechanisms of 
      kinase-phosphatase interactions.
PG  - rs15
LID - 10.1126/scisignal.2004712 [doi]
AB  - The Hippo pathway regulates organ size and tissue homeostasis in response to 
      multiple stimuli, including cell density and mechanotransduction. Pharmacological 
      inhibition of phosphatases can also stimulate Hippo signaling in cell culture. We 
      defined the Hippo protein-protein interaction network with and without inhibition 
      of serine and threonine phosphatases by okadaic acid. We identified 749 protein 
      interactions, including 599 previously unrecognized interactions, and 
      demonstrated that several interactions with serine and threonine phosphatases 
      were phosphorylation-dependent. Mutation of the T-loop of MST2 (mammalian 
      STE20-like protein kinase 2), which prevented autophosphorylation, disrupted its 
      association with STRIPAK (striatin-interacting phosphatase and kinase complex). 
      Deletion of the amino-terminal forkhead-associated domain of SLMAP (sarcolemmal 
      membrane-associated protein), a component of the STRIPAK complex, prevented its 
      association with MST1 and MST2. Phosphatase inhibition produced temporally 
      distinct changes in proteins that interacted with MOB1A and MOB1B (Mps one binder 
      kinase activator-like 1A and 1B) and promoted interactions with upstream Hippo 
      pathway proteins, such as MST1 and MST2, and with the trimeric protein 
      phosphatase 6 complex (PP6). Mutation of three basic amino acids that are part of 
      a phospho-serine- and phospho-threonine-binding domain in human MOB1B prevented 
      its interaction with MST1 and PP6 in cells treated with okadaic acid. 
      Collectively, our results indicated that changes in phosphorylation orchestrate 
      interactions between kinases and phosphatases in Hippo signaling, providing a 
      putative mechanism for pathway regulation.
FAU - Couzens, Amber L
AU  - Couzens AL
AD  - 1Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute at Mount 
      Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
FAU - Knight, James D R
AU  - Knight JD
FAU - Kean, Michelle J
AU  - Kean MJ
FAU - Teo, Guoci
AU  - Teo G
FAU - Weiss, Alexander
AU  - Weiss A
FAU - Dunham, Wade H
AU  - Dunham WH
FAU - Lin, Zhen-Yuan
AU  - Lin ZY
FAU - Bagshaw, Richard D
AU  - Bagshaw RD
FAU - Sicheri, Frank
AU  - Sicheri F
FAU - Pawson, Tony
AU  - Pawson T
FAU - Wrana, Jeffrey L
AU  - Wrana JL
FAU - Choi, Hyungwon
AU  - Choi H
FAU - Gingras, Anne-Claude
AU  - Gingras AC
LA  - eng
GR  - MOP-123433/Canadian Institutes of Health Research/Canada
GR  - MOP-84314/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131119
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (MOB1A protein, human)
RN  - 0 (MOB1B protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (SLMAP protein, human)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.1.11 (STK4 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (STK3 protein, human)
RN  - EC 2.7.11.1 (Serine-Threonine Kinase 3)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (protein phosphatase 6)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Animals
MH  - Binding Sites
MH  - Blotting, Western
MH  - Cluster Analysis
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Luciferases/genetics/metabolism
MH  - Luminescent Proteins/genetics/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Mutation
MH  - Phosphoprotein Phosphatases/genetics/metabolism
MH  - Phosphoric Monoester Hydrolases/classification/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Interaction Mapping/methods
MH  - *Protein Interaction Maps
MH  - Protein Serine-Threonine Kinases/classification/genetics/*metabolism
MH  - Serine-Threonine Kinase 3
MH  - *Signal Transduction
EDAT- 2013/11/21 06:00
MHDA- 2014/08/03 06:00
CRDT- 2013/11/21 06:00
PHST- 2013/11/21 06:00 [entrez]
PHST- 2013/11/21 06:00 [pubmed]
PHST- 2014/08/03 06:00 [medline]
AID - 6/302/rs15 [pii]
AID - 10.1126/scisignal.2004712 [doi]
PST - epublish
SO  - Sci Signal. 2013 Nov 19;6(302):rs15. doi: 10.1126/scisignal.2004712.