Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility.
EDG-1 is a heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet-derived growth factor (PDGF), which stimulates sphingosine kinase and increases intracellular SPP, was dependent on expression of EDG-1. Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine triphosphatase Rac, which is essential for protrusion of lamellipodia and forward movement. Moreover, PDGF activated EDG-1, as measured by translocation of beta-arrestin and phosphorylation of EDG-1. Our results reveal a role for receptor cross-communication in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility.
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
J P
JP
Hobson
H M
HM
Rosenfeldt
L S
LS
Barak
A
A
Olivera
S
S
Poulton
M G
MG
Caron
S
S
Milstien
S
S
Spiegel
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D000077214:Becaplermin; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D017353:Gene Deletion; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008246:Lysophospholipids; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D020239:Receptor Cross-Talk; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D000071557:beta-Arrestins; D000099157:Sphingosine Kinase
D019390:Arrestins; D000077214:Becaplermin; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D017479:Receptors, Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D013110:Sphingosine; D000071557:beta-Arrestins; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate; C061800:N,N-dimethylsphingosine