The functional pDGFβ 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 PDGFβ receptor–S1P1 receptor complex. The S1P1 receptor is constitutively active and functions to enhance PDGF-stimulated migration of MEF. This was based on three pieces of evidence. Firstly, the S1P1 receptor and PDGFβ receptor are co-immunoprecipitated from cell lysates using anti-PDGFβ receptor antibody. These findings suggest that the receptors form a complex in MEF. Secondly, inverse agonism of the S1P1 receptor with SB649146 to eliminate the constitutive activity of the S1P1 receptor reduced the PDGF-induced activation of p42/p44 MAPK in MEF. Thirdly, SB649146 inhibited the migration of MEF in response to the selective S1P1 receptor agonist, SEW2871 or PDGF. In contrast, S1P inhibited PDGF-stimulated MEF migration, possibly mediated by the inhibitory S1P2 receptor. These findings resolve an important issue regarding the functional role of the S1P1 receptor in regulating MEF migration and suggest an important role within the context of PDGFβ receptor–S1P1 receptor complex signaling.