Platelet‐derived growth factor (PDGF)‐induced chemotaxis does not require the G protein‐coupled receptor S1P1 in murine embryonic fibroblasts and vascular smooth muscle cells

FEBS Letters

Kluk, Michael J.¹  Hla, Timothy¹  Colmont, Chantal¹  Wu, Ming-Tao¹ 

[1] Center for Vascular Biology, Department of Physiology, MC3501, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3501, USA

关键词: Sphingosine 1-phosphate;    Vascular smooth muscle cells;    Platelet-derived growth factor;    EDG-1;    S1P1 receptor;    G-protein-coupled receptor;    Receptor tyrosine kinase;    Migration;    Chemotaxis;    Vascular disease;    Vascular development;    S1P;    sphingosine 1-phosphate;    PDGF;    platelet-derived growth factor;    VSMC;    vascular smooth muscle cell;    GPCR;    G protein-coupled receptor;    MAP kinase;    mitogen-activated protein kinase;    MEF;    mouse embryonic fibroblast;    RT-PCR;    reverse transcriptase-polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(02)03742-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, signals via G protein-coupled receptors (GPCR). The prototypical S1P receptor, S1P₁ (also known as EDG-1), a G_i-linked receptor, is critical for vascular maturation during development. Recent work suggested that platelet-derived growth factor (PDGF)-induced cell migration required the S1P₁ receptor, representing a novel mechanism for cross-talk between receptor tyrosine kinases and GPCRs. Since both S1P and PDGF are implicated in vascular smooth muscle cell (VSMC) pathobiology and development, we investigated this issue in rat VSMC and in embryonic fibroblasts derived from S1P₁ null mice. Our data suggest that the S1P₁ receptor is critical for S1P-induced, G_i-dependent migration but not for PDGF-BB-induced, receptor tyrosine kinase-dependent chemotaxis in VSMC. In addition, lack of S1P₁ receptor in mouse embryonic fibroblasts did not significantly affect PDGF-induced cell migration. These data question the generality of the concept that S1P₁ GPCR is a critical downstream component of PDGF-induced chemotaxis.

【 授权许可】

Unknown