PMID- 27097102
OWN - NLM
STAT- MEDLINE
DCOM- 20171212
LR  - 20180118
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 34
IP  - 8
DP  - 2016 Aug
TI  - Quantitative Phosphoproteomic Study Reveals that Protein Kinase A Regulates 
      Neural Stem Cell Differentiation Through Phosphorylation of Catenin Beta-1 and 
      Glycogen Synthase Kinase 3beta.
PG  - 2090-101
LID - 10.1002/stem.2387 [doi]
AB  - Protein phosphorylation is central to the understanding of multiple cellular 
      signaling pathways responsible for regulating the self-renewal and 
      differentiation of neural stem cells (NSCs). Here we performed a large-scale 
      phosphoproteomic analysis of rat fetal NSCs using strong cation exchange 
      chromatography prefractionation and citric acid-assisted two-step enrichment with 
      TiO2 strategy followed by nanoLC-MS/MS analysis. Totally we identified 32,546 
      phosphosites on 5,091 phosphoproteins, among which 23,945 were class I 
      phosphosites, and quantified 16,000 sites during NSC differentiation. More than 
      65% of class I phosphosites were novel when compared with PhosphoSitePlus 
      database. Quantification results showed that the early and late stage of NSC 
      differentiation differ greatly. We mapped 69 changed phosphosites on 20 proteins 
      involved in Wnt signaling pathway, including S552 on catenin beta-1 (Ctnnb1) and 
      S9 on glycogen synthase kinase 3beta (Gsk3beta). Western blotting and real-time PCR 
      results proved that Wnt signaling pathway plays critical roles in NSC fate 
      determination. Furthermore, inhibition and activation of PKA dramatically 
      affected the phosphorylation state of Ctnnb1 and Gsk3beta, which regulates the 
      differentiation of NSCs. Our data provides a valuable resource for studying the 
      self-renewal and differentiation of NSCs. Stem Cells 2016;34:2090-2101.
CI  - (c) 2016 AlphaMed Press.
FAU - Wang, Shuxin
AU  - Wang S
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life 
      Sciences, Beijing, Peoples' Republic of China.
FAU - Li, Zheyi
AU  - Li Z
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life 
      Sciences, Beijing, Peoples' Republic of China.
FAU - Shen, Hongyan
AU  - Shen H
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life 
      Sciences, Beijing, Peoples' Republic of China.
FAU - Zhang, Zhong
AU  - Zhang Z
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life 
      Sciences, Beijing, Peoples' Republic of China.
FAU - Yin, Yuxin
AU  - Yin Y
AD  - Institute of Systems Biomedicine, Peking University Health Science Center, Peking 
      University, Beijing, Peoples' Republic of China.
FAU - Wang, Qingsong
AU  - Wang Q
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life 
      Sciences, Beijing, Peoples' Republic of China.
FAU - Zhao, Xuyang
AU  - Zhao X
AD  - Institute of Systems Biomedicine, Peking University Health Science Center, Peking 
      University, Beijing, Peoples' Republic of China.
FAU - Ji, Jianguo
AU  - Ji J
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life 
      Sciences, Beijing, Peoples' Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160510
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Phosphoproteins)
RN  - 0 (beta Catenin)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Cell Differentiation/drug effects
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Fetus/cytology
MH  - Gene Ontology
MH  - Glycogen Synthase Kinase 3 beta/*metabolism
MH  - Mice
MH  - Molecular Sequence Annotation
MH  - Neural Stem Cells/*cytology/drug effects/metabolism
MH  - Phosphoproteins/chemistry/*metabolism
MH  - Phosphorylation/drug effects
MH  - Proteomics/*methods
MH  - Rats
MH  - Tretinoin/pharmacology
MH  - Wnt Signaling Pathway/drug effects
MH  - beta Catenin/*metabolism
OTO - NOTNLM
OT  - Neural stem cells
OT  - Phosphoproteomics
OT  - Protein kinase A
OT  - TiO2
OT  - Wnt signaling pathway
EDAT- 2016/04/21 06:00
MHDA- 2017/12/13 06:00
CRDT- 2016/04/21 06:00
PHST- 2015/10/24 00:00 [received]
PHST- 2016/03/26 00:00 [accepted]
PHST- 2016/04/21 06:00 [entrez]
PHST- 2016/04/21 06:00 [pubmed]
PHST- 2017/12/13 06:00 [medline]
AID - 10.1002/stem.2387 [doi]
PST - ppublish
SO  - Stem Cells. 2016 Aug;34(8):2090-101. doi: 10.1002/stem.2387. Epub 2016 May 10.