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Voltage‐gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G‐protein Rap
Author(s) -
Potapova Irina A.,
Cohen Ira S.,
Doronin Sergey V.
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05966.x
Subject(s) - angiotensin ii , g protein , receptor , gq alpha subunit , hek 293 cells , microbiology and biotechnology , chemistry , guanine nucleotide exchange factor , signal transduction , ion channel , biology , medicine , biochemistry
The voltage‐gated potassium channel Kv4.3 was coexpressed with its β‐subunit Kv channel‐interacting protein 2 and the angiotensin type 1 receptor in HEK‐293 cells. Proteomic analysis of proteins coimmunoprecipitated with Kv4.3 revealed that Kv4.3 is associated with Rap guanine nucleotide exchange factors MR‐GEF and EPAC‐1. Previously, we demonstrated that Kv4.3 interacts with the angiotensin type 1 receptor in HE293 cells and cardiac myocytes. On the basis of this, we investigated the angiotensin type 1 receptor signaling to small G‐proteins Ras and Rap‐1 in the presence and absence of the Kv4.3–Kv channel‐interacting protein 2 macromolecular complex. Ras activation was not significantly affected by coexpression of Kv4.3 and Kv channel‐interacting protein 2. Ras exhibited a rapid activation–inactivation pattern with maximum activity at 2.5 min after addition of angiotensin II. In contrast, activation of Rap‐1 was affected dramatically by coexpression of Kv4.3 and Kv channel‐interacting protein 2 with the angiotensin type 1 receptor. In the absence of Kv4.3 and Kv channel‐interacting protein 2, stimulation of the angiotensin type 1 receptor resulted in steady activation of Rap‐1 that reached a plateau 25 min after addition of angiotensin II. In the presence of Kv4.3 and Kv channel‐interacting protein 2, Rap‐1 reaches a maximum activity 2.5 min after addition of angiotensin II and then deactivates rapidly, demonstrating a pattern of activation similar to that of Ras. Our findings show that Kv4.3 regulates angiotensin type 1 receptor signaling to the small G‐protein Rap‐1.