TAILIEUCHUNG - Báo cáo khoa học: 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

The voltage-gated potassium channel was coexpressed with itsb-sub-unit Kv channel-interacting protein 2 and the angiotensin type 1 receptor in HEK-293 cells. Proteomic analysis of proteins coimmunoprecipitated with revealed that is associated with Rap guanine nucleotide exchange factors MR-GEF and EPAC-1. | ỊFEBS Journal Voltage-gated ion channel is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G-protein Rap Irina A. Potapova Ira S. Cohen and Sergey V. Doronin Department of Physiology and Biophysics Institute of Molecular Cardiology State University of New York at Stony Brook NY USA Keywords angiotensin receptor type 1 EPAC mR-GEF iTRAQ Correspondence S. Doronin Department of Physiology and Biophysics BST-6 Room 124 University of New York at Stony Brook Stony Brook NY 11794 USA Fax 1 631 444 3432 Tel 1 631 444 7373 E-mail sdoronin@ Received 16 April2007 revised 11 June 2007 accepted 29 June 2007 doi The voltage-gated potassium channel was coexpressed with its b-sub-unit Kv channel-interacting protein 2 and the angiotensin type 1 receptor in HEK-293 cells. Proteomic analysis of proteins coimmunoprecipitated with revealed that is associated with Rap guanine nucleotide exchange factors MR-GEF and EPAC-1. Previously we demonstrated that 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 channel-interacting protein 2 macromolecular complex. Ras activation was not significantly affected by coexpression of and Kv channel-interacting protein 2. Ras exhibited a rapid activation-inactivation pattern with maximum activity at min after addition of angiotensin II. In contrast activation of Rap-1 was affected dramatically by coexpression of and Kv channel-interacting protein 2 with the angiotensin type 1 receptor. In the absence of 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

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