S1P induces FA remodeling in human pulmonary endothelial cells: Role of Rac, GIT1, FAK, and paxillin

Yasushi Shikata, Konstantin G. Birukov, Joe G.N. Garcia

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


Sphingosine 1-phosphate (SIP) enhances human pulmonary endothelial monolayer integrity via Rac GTPase-dependent formation of a cortical actin ring (Garcia et al. J Clin Invest 108: 689-701, 2001). The mechanisms underlying this response are not well understood but may involve rapid redistribution of focal adhesions (FA) as attachment sites for actin filaments. We evaluate the effects of S1P on the redistribution of paxillin, FA kinase (FAK), and the G protein-coupled receptor kinase-interacting proteins (GITs). S1P induced Rac GTPase activation and cortical actin ring formation at physiological concentrations (0.5 μM), whereas 5 μM S1P caused prominent stress fiber formation and activation of Rho and Rac GTPases. SIP (0.5 μM) stimulated the tyrosine phosphorylation of FAK Y576, and paxillin was linked to FA disruption and redistribution to the cell periphery. Furthermore, S1P induced a transient association of GIT1 with paxillin and redistribution of the GIT2-paxillin complex to the cell cortical area without affecting GIT2-paxillin association. These results suggest a role of FA rearrangement in S1P-mediated barrier enhancement via Rac- and GIT-mediated processes.

Original languageEnglish (US)
Pages (from-to)1193-1203
Number of pages11
JournalJournal of Applied Physiology
Issue number3
StatePublished - Mar 1 2003


  • Barrier function
  • Cytoskeleton
  • Human pulmonary endothelium
  • Rho

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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