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Regulation of G‐protein coupled receptor activities by platelet‐endothelial cell adhesion molecule, PECAM‐1
Author(s) -
Yeh Jiunnchern,
Otte Laura,
Frangos John A
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.908.10
Subject(s) - hek 293 cells , gq alpha subunit , microbiology and biotechnology , g protein coupled receptor , transfection , receptor , immunoprecipitation , bradykinin , g protein , protein subunit , scaffold protein , signal transduction , chemistry , biology , cell culture , biochemistry , gene , genetics
Previously, we have shown that G protein alpha subunit Gq/11 is rapidly activated in primary HUVEC upon fluid shear stress stimulation. Here we show that Gq/11 forms a complex with PECAM‐1. In order to understand the role of PECAM‐1 in this complex, we determined the critical regions of PECAM‐1 involved in this interaction. By expressing truncated forms of PECAM‐1 in HEK293 cells, we found that the cytoplasmic domain of PECAM‐1 is not required for its association with Gq/11. Domain swapping of PECAM‐1 with intracellular cell adhesion molecule 1 (ICAM‐1), a protein that does not form a complex with Gq/11, provides evidence that the extracellular domain of PECAM‐1 is critical for this interaction. This result also suggests that PECAM‐1 does not directly interact with Gq/11. Co‐expression of bradykinin receptor B2 (BKRB2), a Gq/11‐coupled receptor, with PECAM‐1 enhances PECAM‐1‐Gq/11 complex formation, suggesting an interaction between PECAM‐1 and BKRB2. Co‐immunoprecipitation experiments indicate that these two molecules indeed form a complex when expressed in HEK293 cells. Activation of ERK1/2 by bradykinin in HUVEC is enhanced when PECAM‐1 expression is inhibited by transfection of small interference RNA against PECAM‐1. Taken together, our results provide evidence of PECAM‐1 interaction with BKRB2 and of its possible role in regulating GPCR and G protein functions. Supported by NIH grant HL40696.