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Delineating Signaling Pathways Involved In Class A Scavenger Receptor‐mediated Cell Adhesion
Author(s) -
Nikolic Dejan M,
Gass C.,
Post S. R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a695-a
Subject(s) - lyn , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , cell adhesion , kinase , chemistry , protein kinase b , src family kinase , scavenger receptor , signal transduction , focal adhesion , biology , cell , biochemistry , lipoprotein , cholesterol
Class A scavenger receptors (SR‐A) participate in multiple macrophage functions including macrophage adhesion to modified forms of extracellular matrix (ECM) proteins. Thus, SR‐A‐mediated adhesion might play a role in macrophage accumulation at sites rich in modified ECM proteins such as sites of chronic inflammation or injury; e.g., atherosclerotic lesions. To define the role of specific signaling pathways in regulating SR‐A mediated adhesion, the attachment and spreading of macrophages isolated from SR‐A+/+ or SR‐A−/ − mice and HEK cells that inducibly express SR‐A, plated on SR‐A ligand was examined. Inhibiting Gi/o proteins with pertussis toxin decreased SR‐A‐mediated cell attachment by 40%, but did not prevent the subsequent spreading of attached cells. In contrast, pretreating cells with inhibitors of PI3‐kinase or Src family kinases abolished SR‐A‐dependent cell spreading without decreasing SR‐A‐mediated cell attachment. In addition, we found that SR‐A‐mediated adhesion activates the Src kinase Lyn, PI3‐kinase and Akt. Inhibiting Src kinase abolished PI3‐kinase activation indicating that Src kinase (Lyn) activation occurs upstream of PI3‐kinase. The selectivity of signals required for SR‐A spreading was confirmed in macrophages from SR‐A−/ − mice, which showed decreased Lyn activation when compared to SR‐A+/+ macrophages. Overall, our results indicate that SR‐A mediates cell adhesion by a process involving the sequential activation of signaling cascades that differentially regulate initial cell attachment (Gi/o proteins) and subsequent cell spreading (Src kinase Lyn, PI3‐kinase, and Akt). Supported by grants from NIH and AHA.