Class A scavenger receptor-mediated cell adhesion requires the sequential activation of Lyn and PI3-kinase

Dejan M. Nikolic, Jill Cholewa, Cecelia Gass, Ming C. Gong, Steven R. Post

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Class A scavenger receptors (SR-A) participate in multiple macrophage functions including macrophage adhesion to modified proteins. SR-A-mediated adhesion may therefore contribute to chronic inflammation by promoting macrophage accumulation at sites of protein modification. The mechanisms that couple SR-A binding to modified proteins with increased cell adhesion have not been defined. In this study, SR-A expressing HEK cells and SR-A+/+ or SR-A-/- macrophages were used to delineate the signaling pathways required for SR-A-mediated adhesion to modified protein. Inhibiting Gi/o activation, which decreases initial SR-A-mediated cell attachment, did not prevent the subsequent spreading of attached cells. In contrast, inhibition of Src kinases or PI3-kinase abolished SR-A-dependent cell spreading without affecting SR-A-mediated cell attachment. Consistent with these results, the Src kinase Lyn and PI3-kinase were sequentially activated during SR-A-mediated cell spreading. Furthermore, activation of both Lyn and PI3-kinase was required for enhancing paxillin phosphorylation. Activation of a Src kinase-PI3-kinase-Akt pathway was also observed in cells expressing a truncated SR-A protein that does not internalize indicating that SR-A-mediated activation of intracellular signaling cascades following adhesion to MDA-BSA is independent of receptor internalization. Thus SR-A binding to modified protein activates signaling cascades that have distinct roles in regulating initial cell attachment and subsequent cell spreading.

Original languageEnglish
Pages (from-to)C1450-C1458
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4
StatePublished - Apr 2007


  • Inflammation
  • Intracellular signaling
  • Macrophage

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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