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Bradykinin B 2 Receptor Interacts with Integrin α5β1 to Transactivate Epidermal Growth Factor Receptor in Kidney Cells
Author(s) -
Kramarenko Inga I,
Bunni Marlene,
Raymond John R,
Garnovskaya Maria N
Publication year - 2008
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.22.1_supplement.829.5
Subject(s) - chemistry , microbiology and biotechnology , integrin , small interfering rna , signal transduction , transactivation , mapk/erk pathway , epidermal growth factor receptor , transfection , epidermal growth factor , receptor , biology , biochemistry , gene , transcription factor
The vasoactive peptide bradykinin (BK) stimulates proliferation of the inner medullary collecting duct (mIMCD‐3) cells via transactivation of epidermal growth factor receptor (EGFR) by an unusual mechanism that involves collagenases‐2 and ‐3. Since collagenases lack an integral membrane domain, we hypothesized that integrins may target collagenases to the membrane to form a functional signaling complex. We supported a role of integrins in BK‐induced signaling by showing that RGD peptides and neutralizing antibody against α5β1 integrin partially (∼50%) decreased BK‐induced phosphorylation of extracellular signal‐regulated protein kinase (ERK) in mIMCD‐3 cells. Silencing of α5 and β1 expression by transfecting cells with siRNA also caused a significant (∼40%) decrease in BK‐induced ERK activation and EGFR phosphorylation. The effect was more pronounced (∼70% inhibition) in cells that were co‐transfected with siRNAs directed against collagenases. Using immunoprecipitation/Western blotting, we demonstrated association of BK B 2 receptor with α5β1 integrin upon BK treatment. Furthermore, we showed that BK induced complex formation between α5β1, collagenases and EGFR. These data provide the first evidence that integrins are involved in BK‐induced proliferation of kidney cells, and might ultimately lead to development of new strategies for treatment of renal tubulointerstitial fibrosis.