The functional PDGFbeta receptor-S1P1 receptor signaling complex is involved in regulating migration of mouse embryonic fibroblasts in response to platelet derived growth factor.
We report here that mouse embryonic fibroblasts (MEF) express a functional PDGFbeta receptor-S1P(1) receptor complex. The S1P(1) receptor is constitutively active and functions to enhance PDGF-stimulated migration of MEF. This was based on three pieces of evidence. Firstly, the S1P(1) receptor and PDGFbeta receptor are co-immunoprecipitated from cell lysates using anti-PDGFbeta receptor antibody. These findings suggest that the receptors form a complex in MEF. Secondly, inverse agonism of the S1P(1) receptor with SB649146 to eliminate the constitutive activity of the S1P(1) receptor reduced the PDGF-induced activation of p42/p44 MAPK in MEF. Thirdly, SB649146 inhibited the migration of MEF in response to the selective S1P(1) receptor agonist, SEW2871 or PDGF. In contrast, S1P inhibited PDGF-stimulated MEF migration, possibly mediated by the inhibitory S1P(2) receptor. These findings resolve an important issue regarding the functional role of the S1P(1) receptor in regulating MEF migration and suggest an important role within the context of PDGFbeta receptor-S1P(1) receptor complex signaling.
Long
Jaclyn S
JS
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK.
Natarajan
Viswanathan
V
Tigyi
Gabor
G
Pyne
Susan
S
Pyne
Nigel J
NJ
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D047468:Immunoprecipitation; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000276:immunology / Q000502:physiology*; D049349:Receptors, Lysosphingolipid / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D020797:Receptor, Platelet-Derived Growth Factor beta; D013110:Sphingosine