Regulation of G Protein-Coupled Receptor Activities by the Platelet-Endothelial Cell Adhesion Molecule, PECAM-1

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• 作者：Jiunn-chern Yeh ; Laura A. Otte ; John A. Frangos
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：August 26, 2008
• 年：2008
• 卷：47
• 期：34
• 页码：9029-9039
• 全文大小：420K
• 年卷期：v.47,no.34(August 26, 2008)
• ISSN：1520-4995

文摘

It is becoming increasingly evident that the cell−cell junction is a major signaling center. Here we show that the Gαq/11 subunit of heterotrimeric G proteins forms a complex with platelet-endothelial cell adhesion molecule 1 (PECAM-1), a junctional protein that has been shown to be involved in mechanosignaling in endothelial cells. 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 human embryonic kidney (HEK293) cells, we found that the cytoplasmic domain of PECAM-1 is not required for its association with Gαq/11. Domain swapping of PECAM-1 with intracellular cell adhesion molecule 1 (ICAM-1), a protein that does not form a complex with Gαq/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 Gαq/11. Coexpression of bradykinin receptor B2 (BKRB2), a Gαq/11-coupled receptor, with PECAM-1 enhances formation of the PECAM-1−Gαq/11 complex, 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 interaction of PECAM-1 with BKRB2 and of its possible role in regulating G protein-coupled receptor (GPCR) and G protein functions.