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Identification of Divergent Regulatory Mechanisms across the RGK Family of Small GTPases
Author(s) -
Kaminski Catherine,
Manning Janet R.,
Magyar Janos,
Shi GengXian,
Sievert Gail,
Satin Jonathan,
Andres Doug
Publication year - 2013
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.27.1_supplement.598.3
Subject(s) - phosphorylation , gtpase , microbiology and biotechnology , kinase , biology , protein kinase a , stimulation , chemistry , endocrinology
The small GTPases Rem, Rem2, Rad, and Gem/Kir (RGK) potently block L‐type calcium current (I Ca,L ) when overexpressed. Multiple RGK proteins are expressed in excitable tissues such as the heart. This study aims to understand how RGK proteins are regulated and how they function physiologically. Analysis of cardiac hypertrophy and I Ca,L in Rem and Rad knockout mice suggests separable functions for these closely related G‐proteins. As a potential regulatory mechanism, Rem phosphorylation by protein kinase D (PKD) after α‐adrenergic stimulation was reported to relieve Rem‐mediated I Ca,L inhibition (Jhun BS et al. Circulation Research 2012; 110:59–70). Using phospho‐Rem and phospho‐Gem specific antibodies, we also observed PKD‐dependent phosphorylation of Rem downstream of α‐adrenergic stimuli. Interestingly, while α‐adrenergic stimulation had no effect on the phosphorylation state of Gem, robust phosphorylation of Gem was achieved downstream of β‐adrenergic stimuli and was dependent on protein kinase A. Together, these studies suggest that individual RGK proteins have divergent roles in I Ca,L modulation and that distinct kinase cascades may allow differential regulation of RGK proteins for fine tuning of I Ca,L control. This work was supported by the National Institutes of Health R01 HL072936 (to DAA and JS) and T32 HL072743 (to CNK).