Regulator of G protein signaling 1 (RGS1) markedly impairs Gi alpha signaling responses of B lymphocytes.
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 alpha subunits and assessed its effect on chemokine signaling. G protein binding and GTPase assays revealed that RGS1 is a Gi alpha and Gq alpha GTPase-activating protein and a potential G12 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 G12 alpha. Furthermore, germinal 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.
Moratz
C
C
B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kang
V H
VH
Druey
K M
KM
Shi
C S
CS
Scheschonka
A
A
Murphy
P M
PM
Kozasa
T
T
Kehrl
J H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019556:COS Cells; D015536:Down-Regulation / Q000276:immunology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D011485:Protein Binding / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D020710:RGS Proteins; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D020690:GTPase-Activating Proteins; D011506:Proteins; D020710:RGS Proteins; C080831:RGS1 protein, human; D011956:Receptors, Cell Surface; C489853:Rgs1 protein, rat; D019206:GTP-Binding Protein alpha Subunits, Gi-Go