PMID- 21949786
OWN - NLM
STAT- MEDLINE
DCOM- 20120130
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 9
DP  - 2011
TI  - Quantitative phosphoproteomics of CXCL12 (SDF-1) signaling.
PG  - e24918
LID - 10.1371/journal.pone.0024918 [doi]
LID - e24918
AB  - CXCL12 (SDF-1) is a chemokine that binds to and signals through the seven 
      transmembrane receptor CXCR4. The CXCL12/CXCR4 signaling axis has been implicated 
      in both cancer metastases and human immunodeficiency virus type 1 (HIV-1) 
      infection and a more complete understanding of CXCL12/CXCR4 signaling pathways 
      may support efforts to develop therapeutics for these diseases. Mass 
      spectrometry-based phosphoproteomics has emerged as an important tool in studying 
      signaling networks in an unbiased fashion. We employed stable isotope labeling 
      with amino acids in cell culture (SILAC) quantitative phosphoproteomics to 
      examine the CXCL12/CXCR4 signaling axis in the human lymphoblastic CEM cell line. 
      We quantified 4,074 unique SILAC pairs from 1,673 proteins and 89 phosphopeptides 
      were deemed CXCL12-responsive in biological replicates. Several well established 
      CXCL12-responsive phosphosites such as AKT (pS473) and ERK2 (pY204) were 
      confirmed in our study. We also validated two novel CXCL12-responsive 
      phosphosites, stathmin (pS16) and AKT1S1 (pT246) by Western blot. Pathway 
      analysis and comparisons with other phosphoproteomic datasets revealed that genes 
      from CXCL12-responsive phosphosites are enriched for cellular pathways such as T 
      cell activation, epidermal growth factor and mammalian target of rapamycin (mTOR) 
      signaling, pathways which have previously been linked to CXCL12/CXCR4 signaling. 
      Several of the novel CXCL12-responsive phosphoproteins from our study have also 
      been implicated with cellular migration and HIV-1 infection, thus providing an 
      attractive list of potential targets for the development of cancer metastasis and 
      HIV-1 therapeutics and for furthering our understanding of chemokine signaling 
      regulation by reversible phosphorylation.
FAU - Wojcechowskyj, Jason A
AU  - Wojcechowskyj JA
AD  - Department of Microbiology, University of Pennsylvania School of Medicine, 
      Philadelphia, Pennsylvania, United States of America.
FAU - Lee, Jessica Y
AU  - Lee JY
FAU - Seeholzer, Steven H
AU  - Seeholzer SH
FAU - Doms, Robert W
AU  - Doms RW
LA  - eng
GR  - T32 AI007632/AI/NIAID NIH HHS/United States
GR  - T32 AI 07632/AI/NIAID NIH HHS/United States
GR  - R01 40880/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110920
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Phosphopeptides)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteome)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Blotting, Western
MH  - Cell Line
MH  - Chemokine CXCL12/*pharmacology
MH  - GTP-Binding Proteins/metabolism
MH  - Humans
MH  - Isotope Labeling
MH  - Molecular Sequence Data
MH  - Phosphopeptides/chemistry/metabolism
MH  - Phosphoproteins/chemistry/*metabolism
MH  - Proteome/chemistry/metabolism
MH  - Proteomics/*methods
MH  - Reproducibility of Results
MH  - Signal Transduction/*drug effects
PMC - PMC3176801
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/09/29 06:00
MHDA- 2012/01/31 06:00
PMCR- 2011/09/20
CRDT- 2011/09/28 06:00
PHST- 2011/06/24 00:00 [received]
PHST- 2011/08/19 00:00 [accepted]
PHST- 2011/09/28 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/01/31 06:00 [medline]
PHST- 2011/09/20 00:00 [pmc-release]
AID - PONE-D-11-11692 [pii]
AID - 10.1371/journal.pone.0024918 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(9):e24918. doi: 10.1371/journal.pone.0024918. Epub 2011 Sep 20.