PMID- 15741218
OWN - NLM
STAT- MEDLINE
DCOM- 20050713
LR  - 20220223
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 12
DP  - 2005 Jun 15
TI  - Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by 
      desensitizing S1P receptors.
PG  - 4736-42
AB  - Mast cells play a central role in inflammatory and immediate-type allergic 
      reactions by secreting a variety of biologically active substances, including 
      sphingosine-1 phosphate (S1P). Sphingosine kinase 1 (SphK1) and formation of S1P, 
      which leads to transactivation of S1P receptors and their downstream signaling 
      pathways, regulates mast-cell functions initiated by cross-linking of the 
      high-affinity immunoglobulin E (IgE) receptor FcepsilonRI. Surprisingly, 
      overexpression of SphK1 in rat basophilic leukemia (RBL)-2H3 mast cells impaired 
      degranulation as well as migration toward antigen. These effects were reversed by 
      serum withdrawal, yet the increased formation and secretion of S1P were the same 
      as in the presence of serum. Nonetheless, serum increased localization of SphK1 
      at the plasma membrane. This restricted formation of S1P induced internalization 
      and desensitization of S1P receptors on the surface of mast cells as determined 
      by confocal immunofluorescence microscopy, aberrant S1P receptor signaling, and 
      lack of S1P receptor coupling to G proteins. Serum starvation, which 
      significantly reduced membrane-associated SphK1 activity, restored S1P receptor 
      functions. Our results have important implications for mast-cell migration and 
      degranulation as well as for the biologic functions of the S1P receptors on cells 
      that are circulating in the bloodstream.
FAU - Jolly, Puneet S
AU  - Jolly PS
AD  - Department of Biochemistry, Virginia Commonwealth University Medical Center, 
      Richmond, VA 23298-0614, USA.
FAU - Bektas, Meryem
AU  - Bektas M
FAU - Watterson, Kenneth R
AU  - Watterson KR
FAU - Sankala, Heidi
AU  - Sankala H
FAU - Payne, Shawn G
AU  - Payne SG
FAU - Milstien, Sheldon
AU  - Milstien S
FAU - Spiegel, Sarah
AU  - Spiegel S
LA  - eng
GR  - AIS0094/AI/NIAID NIH HHS/United States
GR  - P30 CA16059/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050301
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Ligands)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, IgE)
RN  - 0 (Receptors, Lysosphingolipid)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunit, Gi2)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
RN  - EC 3.6.5.1 (Gnai2 protein, rat)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Calcium/metabolism
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - Cell Movement
MH  - Chemotaxis
MH  - Cross-Linking Reagents/pharmacology
MH  - Culture Media, Serum-Free/pharmacology
MH  - Down-Regulation
MH  - GTP-Binding Protein alpha Subunit, Gi2
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/metabolism
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/metabolism
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Immunoglobulin E/chemistry
MH  - Inflammation
MH  - Ligands
MH  - Mast Cells/*metabolism
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phenotype
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/*biosynthesis/*chemistry/metabolism
MH  - Protein Transport
MH  - Proto-Oncogene Proteins/metabolism
MH  - Rats
MH  - Receptors, IgE/chemistry
MH  - Receptors, Lysosphingolipid/*metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - Transfection
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC1894993
EDAT- 2005/03/03 09:00
MHDA- 2005/07/14 09:00
PMCR- 2006/06/15
CRDT- 2005/03/03 09:00
PHST- 2005/03/03 09:00 [pubmed]
PHST- 2005/07/14 09:00 [medline]
PHST- 2005/03/03 09:00 [entrez]
PHST- 2006/06/15 00:00 [pmc-release]
AID - S0006-4971(20)53407-1 [pii]
AID - 01054736 [pii]
AID - 10.1182/blood-2004-12-4686 [doi]
PST - ppublish
SO  - Blood. 2005 Jun 15;105(12):4736-42. doi: 10.1182/blood-2004-12-4686. Epub 2005 
      Mar 1.