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Molecular analysisof interaction of Insulin Receptor‐beta subunit with Angiotensin type II receptor
Author(s) -
Ramdas Maya,
Kolhe Ravindra,
Gavini Nara,
Pulakat Lakshmi
Publication year - 2007
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.21.6.a832
Subject(s) - angiotensin ii , immunoprecipitation , angiotensin ii receptor type 1 , protein subunit , phosphorylation , receptor , insulin receptor , insulin receptor substrate , medicine , chemistry , endocrinology , microbiology and biotechnology , insulin , biology , insulin resistance , biochemistry , gene
Angiotensin II (Ang II) is a hormone implicated in the regulation of blood pressure and in the pathogenesis of hypertension, insulin resistance and metabolic syndrome. The objective of this study is to investigate regulation of Insulin Receptor (IR) signaling by the Angiotensin II receptor (AT2). We analyzed whether the AT2 interacts with the IR in mammalian cells and how such interaction affects IR phosphorylation. Yeast‐two‐hybrid (Y2H) protein‐protein interaction assay and co‐immunoprecipitation studies were employed in this analysis. Y2H analysis showed that a truncated AT2 receptor that spans the amino acids 226–363 interacted strongly with the IR beta‐ subunit. A chimeric AT2‐AT1 receptor in which the third intracellular loop of the AT2 was replaced with that of the AT1 could also interact with the IR‐beta subunit. However, a truncated AT2 in which the C‐terminal cytoplasmic region was deleted did not interact with the IR‐beta. These results suggested that the AT2 could interact with the IR‐beta, and the C‐terminal cytoplasmic domain of AT2 is essential for this interaction. Co‐immunoprecipitation studies showed that transient expression of the AT2 could result in AT2‐IR‐beta complex formation and phophatase‐independent lack of phosphorylation of IR‐beta in CHO cells. Based on these data, we propose receptor level interaction between the AT2 and IR leads to inhibition of phosphorylation of IR in response to transient expression of AT2.