TY - JOUR
T1 - Second messengers regulate RGS2 expression which is targeted to the nucleus
AU - Zmijewski, Jaroslaw W.
AU - Song, Ling
AU - Harkins, Lualhati
AU - Cobbs, Charles S.
AU - Jope, Richard S.
N1 - Funding Information:
We thank Dr. D.R. Forsdyke for generously providing the RGS2 cDNA, and Dr. Janusz Tucholski, Dr. Mathieu Lesort, and Anna Zmijewski for their suggestions and help with various aspects of this project. This research was supported by NIH Grants MH38752 and NS37768. C.S.C. was supported by a Merit Review grant for cancer research.
PY - 2001/12/19
Y1 - 2001/12/19
N2 - Regulators of G-protein Signaling (RGS) proteins attenuate signaling activities of G proteins, and modulation of expression appears to be a primary mechanism for regulating RGS proteins. In human astrocytoma 1321N1 cells RGS2 expression was increased by activation of muscarinic receptors coupled to phosphoinositide signaling with carbachol, or by increased cyclic AMP production, demonstrating that both signaling systems can increase the expression of a RGS family member in a single cell type. Carbachol-stimulated increases in endogenous RGS2 protein levels appeared by immunocytochemical analysis to be largely confined to the nucleus, and this localization was confirmed by Western blot analysis which showed increased nuclear, but not cytosolic, RGS2 after carbachol treatment. Additionally, transiently expressed green fluorescent protein (GFP)-tagged, 6×His-tagged, or unmodified RGS2 resulted in a predominant nuclear localization, as well as a distinct accumulation of RGS2 along the plasma membrane. The intranuclear localization of GFP-RGS2 was confirmed with confocal microscopy. Thus, RGS2 expression is rapidly and transiently increased by phosphoinositide signaling and by cyclic AMP, and endogenous and transfected RGS2 is largely, although not entirely, localized in the nucleus.
AB - Regulators of G-protein Signaling (RGS) proteins attenuate signaling activities of G proteins, and modulation of expression appears to be a primary mechanism for regulating RGS proteins. In human astrocytoma 1321N1 cells RGS2 expression was increased by activation of muscarinic receptors coupled to phosphoinositide signaling with carbachol, or by increased cyclic AMP production, demonstrating that both signaling systems can increase the expression of a RGS family member in a single cell type. Carbachol-stimulated increases in endogenous RGS2 protein levels appeared by immunocytochemical analysis to be largely confined to the nucleus, and this localization was confirmed by Western blot analysis which showed increased nuclear, but not cytosolic, RGS2 after carbachol treatment. Additionally, transiently expressed green fluorescent protein (GFP)-tagged, 6×His-tagged, or unmodified RGS2 resulted in a predominant nuclear localization, as well as a distinct accumulation of RGS2 along the plasma membrane. The intranuclear localization of GFP-RGS2 was confirmed with confocal microscopy. Thus, RGS2 expression is rapidly and transiently increased by phosphoinositide signaling and by cyclic AMP, and endogenous and transfected RGS2 is largely, although not entirely, localized in the nucleus.
KW - Cyclic AMP
KW - G protein
KW - Phosphoinositide signaling
KW - Regulator of G protein signaling
KW - RGS2
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U2 - 10.1016/S0167-4889(01)00144-6
DO - 10.1016/S0167-4889(01)00144-6
M3 - Article
C2 - 11755214
AN - SCOPUS:0035915459
VL - 1541
SP - 201
EP - 211
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 3
ER -