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Differential effects of melatonin and its downstream effector PKC α on subcellular localization of RGS proteins
Author(s) -
Rimler Avi,
Jockers Ralf,
Lupowitz Zippora,
Sampson Sanford R.,
Zisapel Nava
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2005.00290.x
Subject(s) - rgs2 , microbiology and biotechnology , heterotrimeric g protein , protein kinase c , g protein , biology , gq alpha subunit , signal transduction , melatonin , gtpase activating protein , endocrinology
Regulators of G protein signaling (RGS) are proteins that bind specifically to activated G α subunits of heterotrimeric G proteins to terminate signaling by both G α and G β γ subunits. Signal‐induced RGS redistribution may affect their activity in G protein‐mediated signaling. We have previously shown that melatonin and the cell permeable cGMP analog 8‐bromo cGMP, which lead to protein kinase C (PKC) activation, enhanced cytoplasmic distribution of RGS10 and RGS2 in prostate carcinoma PC3‐AR cells. In the present study, we transfected PC3‐AR cells with myc‐tagged G α i/G α q specific RGS proteins RGS2, RGS4 and RGS10 and examined the effects of melatonin, 8‐bromo cGMP and PKC inhibitors on their nuclear‐cytoplasmic partitioning. RGS10 and RGS2 were predominantly localized in the nucleus and perinuclear regions whereas RGS4 was mostly cytoplasmic in the PC3‐AR cells. Melatonin and the cell permeable cGMP analog 8‐bromo cGMP, previously found to activate PKC α in the PC3‐AR cells, enhanced cytoplasmic localization of RGS10 and RGS2 but induced nuclear accumulation of RGS4. The isozyme specific PKC inhibitor GO6976 (PKC α and PKC β 1) but not hispidin (PKC β ) negated the effects of melatonin on RGS10, RGS2 and RGS4 localization. These findings indicate that PKC α , a downstream effector of the melatonin receptor, differentially affects nuclear/cytoplasmic localization of both G α i and G α q specific RGS proteins. These observations provide further insight into melatonin's ability to fine‐tune multiple membrane G‐proteins signaling in cells.