Runx-dependent regulation of G-protein gamma3 expression in T-cells.
Heterotrimeric G-proteins control diverse biological processes by conveying signals from seven-transmembrane receptors to intracellular effectors. Although their signaling roles were originally ascribed to their GTP-bound alpha-subunits, more recent evidence points to the equally active roles played by their betagamma-dimers. To elucidate the individual contributions of their gamma-subtypes, we used a gene targeting approach to show that mice lacking the gamma3-subtype display a defective T-cell dependent immune response. To identify the cellular basis for this defect, we demonstrated that gamma3-mRNA is strongly induced in activated CD4+ T-cells. To determine the mechanism for this regulated expression, we used several strategies to identify the importance of a Runx consensus sequence element in the first intron of the gamma3 gene and the Runx1 protein. Overall, these data provide the first genetic evidence for the tight regulation and involvement of the G protein gamma3-subtype in mounting an effective immune response in mice.
Dubeykovskiy
Alexander
A
Weis Center for Research, Geisinger Clinic, Danville, PA 17822-2614, USA.
McWhinney
Charlene
C
Robishaw
Janet D
JD
D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007438:Introns / Q000235:genetics; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014611:Vaccination
D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D044388:GTP-Binding Protein gamma Subunits; D009841:Oligonucleotides; C493730:Runx3 protein, mouse