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Possible role of Angiotensin II Receptor (AT2) in regulation of Insulin Receptor signaling
Author(s) -
Ramdas Maya,
Kolhe Ravindra,
Gavini Nara,
Pulakat Lakshmi
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.723.4
Subject(s) - angiotensin ii , insulin receptor , chinese hamster ovary cell , angiotensin ii receptor type 1 , receptor , signal transduction , microbiology and biotechnology , transfection , phosphorylation , biology , endocrinology , medicine , insulin , chemistry , insulin resistance , cell culture , biochemistry , genetics
Renin angiotensin system plays an important role in the development of metabolic syndrome, primarily characterized by insulin resistance, which poses a potential risk for other factors like obesity, hypertension etc. The actions of angiotensin II mediated through the AT1 receptor are well studied, but the role of the AT2 receptor is not clearly established. We have shown that the AT2 can interact with the beta subunit of Insulin Receptor (IR) in yeast two‐hybrid assay. To further evaluate the effects of AT2 on the signaling mechanism of IR, we studied the interaction between the two proteins in Chinese Hamster Ovary (CHO) cells and the human breast cancer (MCF‐7) cells. In our studies using CHO cells, we showed that transient transfection of the AT2 could result in AT2‐IR complex formation and lack of phosphorylation of IR‐beta. However, a truncated AT2 in which C‐terminal cytoplasmic region was deleted did not show interaction with the IR‐beta. MCF‐7 cells constitutively express the AT1 receptor. We have seen that starving these cells for 6 hours or more changes the expression pattern and the levels of the AT1 goes down while the levels of the AT2 increases. These cells expressing the AT2 receptor show lack of phosphorylation of the IR‐beta. Based on these data, we plan to study the proteomics in these cells to further understand the cross talk between angiotensin II and insulin signaling at a cellular and molecular level.

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