Work

B‐Myb regulates the A2B adenosine receptor in vascular smooth muscle cells

Year: 2007

Type: article

Abstract: The A(2B) adenosine receptor (A(2B)AR) has been described to control various vascular functions, including inhibition of smooth muscle cell proliferation. Here, we sought to understand the regulation of A(2B)AR gene expression in aortic vascular smooth muscle cells (VSMCs), with a focus on the proliferation phase. Assays with A(2B)AR-beta-gal aortic VSMCs, in which the endogenous A(2B)AR gene promoter drives the expression of prokaryotic beta-galactosidase (beta-gal) instead of the endogenous A(2B)AR gene, show that beta-gal expression is upregulated when the cells are induced to exit from cell cycle arrest. Similarly, the level of A(2B)AR mRNA is upregulated in proliferating primary aortic VSMCs. In search of related mechanisms, it was noted that the A(2B)AR gene promoter contains several putative binding sites for the proliferation-inducing transcription factor, B-Myb. Using a clone of the 5' region upstream of the mouse A(2B)AR gene linked to a reporter gene, B-Myb site deletion mutants were generated. It was determined that B-Myb upregulates the A(2B)AR gene promoter, and specific promoter binding sites were identified as functional. In accordance, B-Myb also elevates endogenous A(2B)AR mRNA and receptor activity, and this activity decreases cell proliferation. Our data are novel in that they show that this proliferation-inhibiting A(2B)AR is itself an inducible receptor regulated by B-Myb.

Source: Journal of Cellular Biochemistry

DOI: 10.1002/jcb.21586

Authors: Cynthia St. Hilaire, Dan Yang, Barbara M. Schreiber, Katya Ravid

Institution: Boston University

Language: English

Topic: Adenosine and Purinergic Signaling

Subfield: Physiology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: American Heart Association, National Institutes of Health, National Heart, Lung, and Blood Institute