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PMID:21349584

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Citation

Kim, Y, Kim, K, Park, D, Eom, S, Park, H, Lee, H, Lee, YS, Choe, J, Hahn, JH, Kim, YM, Ro, JY and Jeoung, D (2011) Integrin α(5) interacts with EGFR, is necessary for FcɛRI signaling and is necessary for allergic inflammation in relation with angiogenesis. Mol. Immunol. 48:1035-45

Abstract

Recent reports have suggested role for epidermal growth factor receptor (EGFR) in asthma and skin inflammation. Integrin(s) are known to be necessary for the transactivation of EGFR. The roles of EGFR and integrin(s) in allergic inflammation were investigated. Antigen stimulation induced activation of EGFR and interaction between EGFR and integrin α(5) in Rat Basophilic Leukemia (RBL2H3) cells and bone marrow-derived mouse mast cells (BMMCs). Flow cytometry revealed increased phosphorylation of EGFR on cell surfaces. Antigen stimulation induced interaction between EGFR and FcɛRI in both RBL2H3 cells and BMMCs. Blocking of EGFR or integrin α exerted negative effects on rac1 activity and secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α(5) were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with FcɛRI upon antigen stimulation, and it was necessary for the increased secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α(5) were necessary for interactions between activated RBL2H3 cells, BMMCs and rat aortic endothelial cells (RAECs). Conditioned medium of antigen-stimulated RBL2H3 cells promoted RAECs tube formation, rat aortic ring formation and blood vessel formation. Conditioned medium of antigen-stimulated BMMCs also had the same effects on RAECs. This enhanced angiogenic potential of RAECs was dependent on EGFR and integrin α(5). In conclusion, EGFR, via interaction with FcɛRI and integrin α(5), is necessary for allergic inflammation associated with cellular interaction.

Links

PubMed Online version:10.1016/j.molimm.2011.01.013

Keywords

Animals; Asthma/metabolism; Asthma/physiopathology; Blotting, Western; Cell Line, Tumor; Cells, Cultured; Female; Flow Cytometry; Focal Adhesion Protein-Tyrosine Kinases/metabolism; Integrin alpha5/metabolism; Male; Mast Cells/metabolism; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic/physiology; Phosphorylation; Protein Binding; Rats; Rats, Sprague-Dawley; Receptor, Epidermal Growth Factor/metabolism; Receptors, IgE/metabolism; Signal Transduction/physiology; beta-N-Acetylhexosaminidases/metabolism; rac1 GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:A0A0G2K1E2

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2543

F

Seeded From UniProt

complete

RAT:D4A4Y3

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2543

F

Seeded From UniProt

complete

RAT:G3V6K6

enables

GO:0005178: integrin binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2925

F

Seeded From UniProt

complete

RAT:G3V6K6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2307

F

Seeded From UniProt

complete

RAT:G3V6K6

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:1311999

F

Seeded From UniProt

complete

RAT:G3V6K6

located_in

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:Q9QX70

enables

GO:0005178: integrin binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2925

F

Seeded From UniProt

complete

RAT:Q9QX70

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2307

F

Seeded From UniProt

complete

RAT:Q9QX70

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:1311999

F

Seeded From UniProt

complete

RAT:Q9QX70

located_in

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CD44

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2543

F

Seeded From UniProt

complete


See also

References

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