Premium
Crosstalk between 5‐HT 2A receptor and EGFR involves integrins
Author(s) -
Gooz Monika,
Gooz Pal,
Raymond John 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.a247-d
Subject(s) - integrin , crosstalk , mapk/erk pathway , chemistry , receptor , extracellular matrix , proximity ligation assay , microbiology and biotechnology , antibody , signal transduction , immunology , biology , biochemistry , physics , optics
cellular proliferation induced by the 5‐HT 2A receptor in renal mesangial cells. As TACE has a disintegrin domain that may induce ligation of the extracellular matrix (ECM) receptors integrins, next we aimed to investigate the involvement of integrins in GPCR‐EGFR cross‐talk. We pretreated mesangial cells for 1 hr with RGD peptides, which are known to interfere with integrin binding to ECM, prior to treatment with 1 μM 5‐HT or 1 ng/ml EGF for 10 minutes. Cyclic RGD peptide (but not control peptide) completely attenuated the ERK activation induced by 5‐HT or EGF. Using gene array and a human integrin RT‐PCR profiling kit we identified multiple forms of α‐(1‐5, 7‐8, 10, 11, V) and β‐(1,3,5,7) integrin mRNAs in mesangial cells. Next, we tried to inhibit 5‐HT‐mediated ERK activation by using neutralizing antibodies. We pretreated the mesangial cells for 1 hr with the selected antibodies prior to stimulation with 1 μM 5‐HT for 10 minutes and assessed the ERK‐P in Western blotting. We achieved the most effective inhibition by anti‐α5 (45%), ‐αV (77%), ‐β1 (50%) ‐β3 (30%) and anti‐β5 (95%) antibodies compared to normal IgG controls. Our data strongly support the role of integrin ligation in the 5‐HT 2A ‐EGFR crosstalk. This work was supported by NIH 1K01 DK070054‐01 to M.G. and SC COBRE for Cardiovascular Disease NIH NCCR P20 RR016434 to P.G.