PMID- 24260264
OWN - NLM
STAT- MEDLINE
DCOM- 20140711
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - New function of the adaptor protein SH2B1 in brain-derived neurotrophic 
      factor-induced neurite outgrowth.
PG  - e79619
LID - 10.1371/journal.pone.0079619 [doi]
LID - e79619
AB  - Neurite outgrowth is an essential process for the establishment of the nervous 
      system. Brain-derived neurotrophic factor (BDNF) binds to its receptor TrkB and 
      regulates axonal and dendritic morphology of neurons through signal transduction 
      and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular 
      signaling in various physiological processes. The purpose of this study is to 
      investigate the role of SH2B1 in the development of the central nervous system. 
      In this study, we show that knocking down SH2B1 reduces neurite formation of 
      cortical neurons whereas overexpression of SH2B1beta promotes the development of 
      hippocampal neurons. We further demonstrate that SH2B1beta promotes BDNF-induced 
      neurite outgrowth and signaling using the established PC12 cells stably 
      expressing TrkB, SH2B1beta or SH2B1beta mutants. Our data indicate that overexpressing 
      SH2B1beta enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. 
      Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest 
      that these two pathways are required for SH2B1beta-promoted BDNF-induced neurite 
      outgrowth. Moreover, SH2B1beta enhances BDNF-stimulated phosphorylation of signal 
      transducer and activator of transcription 3 at serine 727. Finally, our data 
      indicate that the SH2 domain and tyrosine phosphorylation of SH2B1beta contribute to 
      BDNF-induced signaling pathways and neurite outgrowth. Taken together, these 
      findings demonstrate that SH2B1beta promotes BDNF-induced neurite outgrowth through 
      enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.
FAU - Shih, Chien-Hung
AU  - Shih CH
AD  - Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, 
      Republic of China.
FAU - Chen, Chien-Jen
AU  - Chen CJ
FAU - Chen, Linyi
AU  - Chen L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131115
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (SH2B1 protein, rat)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Hippocampus
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - Neurites
MH  - PC12 Cells
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
PMC - PMC3829828
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/22 06:00
MHDA- 2014/07/12 06:00
PMCR- 2013/11/15
CRDT- 2013/11/22 06:00
PHST- 2013/07/03 00:00 [received]
PHST- 2013/10/03 00:00 [accepted]
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2014/07/12 06:00 [medline]
PHST- 2013/11/15 00:00 [pmc-release]
AID - PONE-D-13-27379 [pii]
AID - 10.1371/journal.pone.0079619 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 15;8(11):e79619. doi: 10.1371/journal.pone.0079619. 
      eCollection 2013.