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Soluble anti‐beta1 integrin antibody induces phosphorylation of focal adhesion kinase and protein kinase B/AKT in mouse aortic endothelial cells
Author(s) -
Schneider Ryan A,
Stevens Rachel L,
Hoyt Dale G
Publication year - 2007
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.21.6.a1153-b
Subject(s) - protein kinase b , integrin , focal adhesion , antibody , chemistry , phosphorylation , kinase , microbiology and biotechnology , signal transduction , cancer research , receptor , biology , biochemistry , immunology
We previously showed that engagement of integrins with soluble antibody protects endothelial cells (EC) from drug‐induced DNA damage. Attachment of cells to surfaces coated with integrin ligands is known to activate focal adhesion kinase (FAK). More recently, it has been found that this attachment can activate pro‐survival signaling via protein kinase B (PKB)/AKT. Here we hypothesized that engagement with soluble anti‐beta1 (B1) integrin antibody would activate these signals. Mouse aortic endothelial cells (MAEC) were incubated in medium containing 0.5% FBS for 20 hours and treated with 1 or 10 ug anti‐B1 antibody/ml or non‐immune IgG for 30 minutes. Protein was then extracted for western blotting with phospho‐specific antibodies. The ratio of phosphoserine 473‐AKT to total AKT increased 1.3‐ and 1.6‐fold in MAEC treated with 1 and 10 ug anti‐B1 antibody/ml respectively compared to the control antibody. In addition, 10 ug anti‐B1 antibody/ml caused a 1.6‐fold increase in the ratio of phosphotyrosine 397‐FAK to total FAK. The results indicate that a soluble anti‐B1 antibody can activate protective outside‐in signaling pathways. The efficacy of soluble integrin agents suggest that these receptors might be manipulated for vascular targeted therapies.