Premium
PKC Activation Leads to Increased RGS2 Protein Levels
Author(s) -
Aschermann Lauren,
Sjogren Benita
Publication year - 2015
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.29.1_supplement.618.16
Subject(s) - rgs2 , regulator of g protein signaling , protein kinase c , activator (genetics) , g protein , microbiology and biotechnology , g protein coupled receptor , signal transduction , chemistry , regulator , phorbol , biology , receptor , gtpase activating protein , biochemistry , gene
Regulator of G protein Signaling 2 (RGS2) is a member of a family of proteins that regulate G protein‐coupled receptor (GPCR) mediated signaling by accelerating GTP hydrolysis on active Gα subunits. RGS2 has been indicated to play an important role in regulating cardiovascular function. RGS2 ‐/‐ mice are hypertensive, are prone to heart failure and show increased responses to vasoconstrictors, such as Angiotensin II. Strategies to increase RGS2 protein levels could thus be a beneficial therapeutic strategy. More detailed information on how RGS2 protein levels are regulated would facilitate these drug discovery efforts. A previous high‐throughput cell‐based screen of natural product extracts identified Indolactam V (ILV), a known PKC activator, to selectively increase protein levels of RGS2. Utilizing the PathHunter ProLabel assay; a β‐galatosidase complementation assay that measures relative protein levels, we found that ILV, as well as phorbol 12‐myristate 13‐acetate (PMA), selectively increase RGS2 protein levels in a time and concentration dependent manner. This effect was blocked by PKC inhibitors indicating a mechanism mediated by PKC. Stimulation of a Gq coupled receptor also results in an increase in RGS2 protein, indicating that this could be a novel feedback mechanism for Gq signaling. This study is continuing to dissect the mechanism by which PKC activation leads to increased RGS2 protein levels. Overall, these studies will lead to increased understanding of how RGS2 protein levels are regulated.