Cancer-Related Somatic Mutations in Transmembrane Helices Alter Adenosine A1 Receptor Pharmacology.

ABSTRACT: Overexpression of the adenosine A₁ receptor (A₁AR) has been detected in various cancer cell lines. However, the role of A₁AR in tumor development is still unclear. Thirteen A₁AR mutations were identified in the Cancer Genome Atlas from cancer patient samples. We have investigated the pharmacology of the mutations located at the 7-transmembrane domain using a yeast system. Concentration-growth curves were obtained with the full agonist CPA and compared to the wild type hA₁AR. H78L^3.23 and S246T^6.47 showed increased constitutive activity, while only the constitutive activity of S246T^6.47 could be reduced to wild type levels by the inverse agonist DPCPX. Decreased constitutive activity was observed on five

SUBMITTER: Wang X 

PROVIDER: S-EPMC9229843 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature