Regulator of G protein signaling 1 (RGS1) markedly impairs Giα signaling responses of B lymphocytes

被引:98
作者
Moratz, C
Kang, VH
Druey, KM
Shi, CS
Scheschonka, A
Murphy, PM
Kozasa, T
Kehrl, JH
机构
[1] NIAID, Immunoregulat Lab, B Cell Mol Immunol Sect, NIH, Bethesda, MD 20892 USA
[2] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA
[3] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA
关键词
D O I
10.4049/jimmunol.164.4.1829
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Regulator of G protein signaling (RGS) proteins modulate signaling through pathways that use heterotrimeric G proteins as transducing elements. RGS1 is expressed at high levels in certain B cell lines and can be induced in normal B cells by treatment with TNF-alpha. To determine the signaling pathways that RGS1 may regulate, we examined the specificity of RGS1 for various G, subunits and assessed its effect on chemokine signaling. G protein binding and GTPase assays revealed that RGS1 is a G,, and G(q alpha) GTPase-activating protein and a potential G(12 alpha) effector antagonist, Functional studies demonstrated that RGS1 impairs platelet activating factor-mediated increases in intracellular Ca+2, stromal-derived factor-1-induced cell migration, and the induction of downstream signaling by a constitutively active form of G(12 alpha). Furthermore, germinial center B lymphocytes, which are refractory to stromal-derived factor-1-triggered migration, express high levels of RGS1, These results indicate that RGS proteins can profoundly effect the directed migration of lymphoid cells.
引用
收藏
页码:1829 / 1838
页数:10
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