The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation

Sravan K. Goparaju, Puneet S. Jolly, Kenneth R. Watterson, Meryem Bektas, Sergio Alvarez, Sukumar Sarkar, Lin Mel, Isao Ishii, Jerold Chun, Sheldon Milstien, Sarah Spiegel

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is the ligand for five specific G protein-coupled receptors, named S1P1 to S1P5. In this study, we found that cross-communication between platelet-derived growth factor receptor and S1P2 serves as a negative damper of PDGF functions. Deletion of the S1P2 receptor dramatically increased migration of mouse embryonic fibroblasts toward S1P, serum, and PDGF but not fibronectin. This enhanced migration was dependent on expression of S1P1 and sphingosine kinase 1 (SphK1), the enzyme that produces S1P, as revealed by downregulation of their expression with antisense RNA and small interfering RNA, respectively. Although S1P2 deletion had no significant effect on tyrosine phosphorylation of the PDGF receptors or activation of extracellular signal-regulated kinase 1/2 or Akt induced by PDGF, it reduced sustained PDGF-dependent p38 phosphorylation and markedly enhanced Rac activation. Surprisingly, S1P2-null cells not only exhibited enhanced proliferation but also markedly increased SphK1 expression and activity. Conversely, reintroduction of S1P2 reduced DNA synthesis and expression of SphK1. Thus, S1P2 serves as a negative regulator of PDGF-induced migration and proliferation as well as SphK1 expression. Our results suggest that a complex interplay between PDGFR and S1P receptors determines their functions.

Original languageEnglish
Pages (from-to)4237-4249
Number of pages13
JournalMolecular and Cellular Biology
Volume25
Issue number10
DOIs
Publication statusPublished - 2005 May
Externally publishedYes

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Lysosphingolipid Receptors
Platelet-Derived Growth Factor
Platelet-Derived Growth Factor Receptors
Phosphorylation
Antisense RNA
Null Lymphocytes
Sphingolipids
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
G-Protein-Coupled Receptors
Fibronectins
Small Interfering RNA
Tyrosine
Down-Regulation
Fibroblasts
Communication
Ligands
sphingosine kinase
DNA
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Goparaju, S. K., Jolly, P. S., Watterson, K. R., Bektas, M., Alvarez, S., Sarkar, S., ... Spiegel, S. (2005). The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation. Molecular and Cellular Biology, 25(10), 4237-4249. https://doi.org/10.1128/MCB.25.10.4237-4249.2005

The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation. / Goparaju, Sravan K.; Jolly, Puneet S.; Watterson, Kenneth R.; Bektas, Meryem; Alvarez, Sergio; Sarkar, Sukumar; Mel, Lin; Ishii, Isao; Chun, Jerold; Milstien, Sheldon; Spiegel, Sarah.

In: Molecular and Cellular Biology, Vol. 25, No. 10, 05.2005, p. 4237-4249.

Research output: Contribution to journalArticle

Goparaju, SK, Jolly, PS, Watterson, KR, Bektas, M, Alvarez, S, Sarkar, S, Mel, L, Ishii, I, Chun, J, Milstien, S & Spiegel, S 2005, 'The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation', Molecular and Cellular Biology, vol. 25, no. 10, pp. 4237-4249. https://doi.org/10.1128/MCB.25.10.4237-4249.2005
Goparaju, Sravan K. ; Jolly, Puneet S. ; Watterson, Kenneth R. ; Bektas, Meryem ; Alvarez, Sergio ; Sarkar, Sukumar ; Mel, Lin ; Ishii, Isao ; Chun, Jerold ; Milstien, Sheldon ; Spiegel, Sarah. / The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 10. pp. 4237-4249.
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