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S1PR1 Tyr143 Phosphorylation Downregulates Endothelial Cell Surface S1PR1 Expression And Responsiveness
Alejandra Chavez, T. Schmidt, Pascal Yazbeck, C. Rajput, B. Desai, S. Sukriti, Kristina Giantsos-Adams, Nebojsa Knezevic, A. Malik, D. Mehta
Published 2015 · Biology, Medicine
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ABSTRACT Activation of sphingosine-1-phosphate receptor 1 (S1PR1) plays a key role in repairing endothelial barrier function. We addressed the role of phosphorylation of the three intracellular tyrosine residues of S1PR1 in endothelial cells in regulating the receptor responsiveness and endothelial barrier function regulated by sphingosine 1-phosphate (S1P)-mediated activation of S1PR1. We demonstrated that phosphorylation of only Y143 site was required for S1PR1 internalization in response to S1P. Maximal S1PR1 internalization was seen in 20 min but S1PR1 returned to the cell surface within 1 h accompanied by Y143-dephosphorylation. Cell surface S1PR1 loss paralleled defective endothelial barrier enhancement induced by S1P. Expression of phospho-defective (Y143F) or phospho-mimicking (Y143D) mutants, respectively, failed to internalize or showed unusually high receptor internalization, consistent with the requirement of Y143 in regulating cell surface S1PR1 expression. Phosphorylation of the five S1PR1 C-terminal serine residues did not affect the role of Y143 phosphorylation in signaling S1PR1 internalization. Thus, rapid reduction of endothelial cell surface expression of S1PR1 subsequent to Y143 phosphorylation is a crucial mechanism of modulating S1PR1 signaling, and hence the endothelial barrier repair function of S1P.
This paper references
Homomeric interactions between type II transforming growth factor-beta receptors.
R. Chen (1994)
Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor
J. Hanke (1996)
Role of β-Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor Internalization
S. Ferguson (1996)
Discovery of a novel , potent , and Src familyselective tyrosine kinase inhibitor . Study of Lckand FynTdependent T cell activation
J. H. Hanke (1996)
Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1.
M. J. Lee (1998)
Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor
M. J. Lee (1998)
Sphingosine - 1 - phosphate as a ligand for the G protein - coupled receptor EDG1
M. J. Lee (1998)
Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1.
C. Liu (1999)
Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors.
X. Zhu (1999)
Sphingosine 1-phosphate stimulates tyrosine phosphorylation of focal adhesion kinase and chemotactic motility of endothelial cells via the G(i) protein-linked phospholipase C pathway.
O. Lee (2000)
Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3
H. Okamoto (2000)
SHP2 Association with VE-Cadherin Complexes in Human Endothelial Cells Is Regulated by Thrombin*
J. A. Ukropec (2000)
An improved high-performance liquid chromatographic method for the determination of sphingosine-1-phosphate in complex biological materials
Lars Ruwisch (2001)
Sphingosine 1-Phosphate-induced Endothelial Cell Migration Requires the Expression of EDG-1 and EDG-3 Receptors and Rho-dependent Activation of αvβ3- and β1-containing Integrins*
J. H. Paik (2001)
Sphingosine 1-phosphate-induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of alpha vbeta3- and beta1-containing integrins.
J. Paik (2001)
Protein Kinase C-α Signals Rho-Guanine Nucleotide Dissociation Inhibitor Phosphorylation and Rho Activation and Regulates the Endothelial Cell Barrier Function*
D. Mehta (2001)
Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement.
J. Garcia (2001)
N‐Glycans of sphingosine 1‐phosphate receptor Edg‐1 regulate ligand‐induced receptor internalization
T. Kohno (2002)
Cutting Edge: Suppression of T Cell Chemotaxis by Sphingosine 1-Phosphate1
M. Graeler (2002)
The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals.
L. Luttrell (2002)
Dual Regulation of EDG1/S1P1 Receptor Phosphorylation and Internalization by Protein Kinase C and G-protein-coupled Receptor Kinase 2*
K. Watterson (2002)
S1P induces FA remodeling in human pulmonary endothelial cells: role of Rac, GIT1, FAK, and paxillin.
Y. Shikata (2003)
Sphingosine-1-phosphate: an enigmatic signalling lipid
S. Spiegel (2003)
Involvement of site‐specific FAK phosphorylation in sphingosine‐1 phosphate‐ and thrombin‐induced focal adhesion remodeling: role of Src and GIT
Y. Shikata (2003)
Physiological and pathological actions of sphingosine 1-phosphate.
T. Hla (2004)
Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury.
B. McVerry (2004)
Endothelial cell barrier regulation by sphingosine 1‐phosphate
B. McVerry (2004)
The immunosuppressant FTY720 down‐regulates sphingosine 1‐phosphate G protein‐coupled receptors
Markus H. Gräler (2004)
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
M. Matloubian (2004)
Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury.
X. Peng (2004)
The immunosuppressant FTY720 downregulates sphingosine 1-phosphate G-protein-coupled receptors
M. H. Gräler (2004)
c-Src is involved in regulating signal transmission from PDGFbeta receptor-GPCR(s) complexes in mammalian cells.
C. Waters (2005)
Sphingosine 1-Phosphate-induced Mobilization of Intracellular Ca2+ Mediates Rac Activation and Adherens Junction Assembly in Endothelial Cells*
D. Mehta (2005)
GRKs and β-arrestins: roles in receptor silencing, trafficking and signaling
E. Reiter (2006)
GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling.
E. Reiter (2006)
Suppression of RhoA Activity by Focal Adhesion Kinase-induced Activation of p190RhoGAP
Michael Holinstat (2006)
Suppression of RhoA activity by focal adhesion kinaseinduced activation of p190RhoGAP: role in regulation of endothelial permeability
M. Holinstat (2006)
Gαq-TRPC6-mediated Ca2+ Entry Induces RhoA Activation and Resultant Endothelial Cell Shape Change in Response to Thrombin*
I. Singh (2007)
Immunosuppressive and Anti-angiogenic Sphingosine 1-Phosphate Receptor-1 Agonists Induce Ubiquitinylation and Proteasomal Degradation of the Receptor*
M. Oo (2007)
Role of Protein Tyrosine Phosphatase 1B in Vascular Endothelial Growth Factor Signaling and Cell–Cell Adhesions in Endothelial Cells
Y. Nakamura (2008)
Activation of Sphingosine Kinase-1 Reverses the Increase in Lung Vascular Permeability Through Sphingosine-1-Phosphate Receptor Signaling in Endothelial Cells
M. Tauseef (2008)
VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF
A. Nottebaum (2008)
Phosphotyrosine protein dynamics in cell membrane rafts of sphingosine-1-phosphate-stimulated human endothelium: role in barrier enhancement.
Jing Zhao (2009)
The G protein bg subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin
N. Knezevic (2009)
The G protein βγ subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin
Nebojsa Knezevic (2009)
Tyrosine sulphation of sphingosine 1-phosphate 1 (S1P1) is required for S1P-mediated cell migration in primary cultures of human umbilical vein endothelial cells.
Yuan-Li Huang (2009)
Regulation of vascular permeability by sphingosine 1-phosphate.
L. Wang (2009)
Balance of S1P1 and S1P2 signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature.
Jen-Fu Lee (2009)
EGFR and ADAMs cooperate to regulate shedding and endocytic trafficking of the desmosomal cadherin desmoglein 2.
Jodi L. Klessner (2009)
Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics
S. Thangada (2010)
S1P1 and VEGFR-2 form a signaling complex with extracellularly regulated kinase 1/2 and protein kinase C-alpha regulating ML-1 thyroid carcinoma cell migration.
N. Bergelin (2010)
S1P1 and VEGFR-2 Form a Signaling Complex with Extracellularly Regulated Kinase 1/2 and Protein Kinase C-α Regulating ML-1 Thyroid Carcinoma Cell Migration
N. Bergelin (2010)
Sphingosine-1-phosphate signaling in vasculogenesis and angiogenesis.
K. Argraves (2010)
Engagement of S1P₁-degradative mechanisms leads to vascular leak in mice.
M. Oo (2011)
Heterotrimeric G proteins, focal adhesion kinase, and endothelial barrier function.
Tracy Thennes (2012)
Crystal Structure of a Lipid G Protein–Coupled Receptor
M. Hanson (2012)
Role of FAK in S1P-regulated endothelial permeability.
P. Belvitch (2012)
The tyrosine phosphatase SHP2 regulates recovery of endothelial adherens junctions through control of β-catenin phosphorylation
Ilse Timmerman (2012)
Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation
Christopher S Garris (2013)
The structure and function of the S1P1 receptor.
C. O’Sullivan (2013)
Dynamin 2–dependent endocytosis is required for sustained S1PR1 signaling
T. Willinger (2014)
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CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function
D. Mao (2021)
Programming to S1PR1+ Endothelial Cells Promotes Restoration of Vascular Integrity
Md. Zahid Akhter (2021)
aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete β-arrestin-2 mediated SphK1-S1PR1-Akt signaling axis
Olivia Molinar-Inglis (2021)
Lipid rafts as platforms for sphingosine 1-phosphate metabolism and signalling.
Chiara D'Aprile (2021)
Sphingosine 1 Phosphate (S1P) Receptor 1 Is Decreased in Human Lung Microvascular Endothelial Cells of Smokers and Mediates S1P Effect on Autophagy
K. Goel (2021)
Circuit Integration Initiation of New Hippocampal Neurons in the Adult Brain.
Chih-Hao Yang (2020)
Advancements in understanding the role of lysophospholipids and their receptors in lung disorders including bronchopulmonary dysplasia.
Tara Sudhadevi (2020)
Post-translational modifications of S1PR1 and endothelial barrier regulation.
Mumtaz Anwar (2020)
Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling
Vijay Avin Balaji Ragunathrao (2019)
Phosphatidic acid in membrane rearrangements
Mikhail A. Zhukovsky (2019)
Mind the gap: mechanisms regulating the endothelial barrier
M. Radeva (2018)
'Crystal' Clear? Lysophospholipid Receptor Structure Insights and Controversies.
V. Blaho (2018)
S1P1 receptor phosphorylation, internalization, and interaction with Rab proteins: effects of sphingosine 1-phosphate, FTY720-P, phorbol esters, and paroxetine
Juan Carlos Martínez-Morales (2018)
Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability.
Y. Komarova (2017)
Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells
N. Pyne (2017)
Signaling Mechanisms Regulating Vascular Endothelial Barrier Function
M. Tauseef (2017)
Transient receptor potential channel 1 maintains adherens junction plasticity by suppressing sphingosine kinase 1 expression to induce endothelial hyperpermeability
M. Tauseef (2016)