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The WD40 repeat protein WDR26 binds G?? and promotes G??-dependent signal transduction and leukocyte migration.

ABSTRACT: The G?? subunits of heterotrimeric G proteins transmit signals to control many cellular processes, including leukocyte migration. G?? signaling may regulate and be regulated by numerous signaling partners. Here, we reveal that WDR26, a member of the WD40 repeat protein family, directly bound free G?? in vitro, and formed a complex with endogenous G?? in Jurkat T cells stimulated by the chemokine SDF1?. Suppression of WDR26 by siRNAs selectively inhibited G??-dependent phospholipase C? and PI3K activation, and attenuated chemotaxis in Jurkat T cells and differentiated HL60 cells in vitro and Jurkat T cell homing to lymphoid tissues in scid mice. Similarly, disruption of the WDR26/G?? interaction via expression of a WDR26 deletion mutant impaired G?? signaling and Jurkat T cell migration, indicating that the function of WDR26 depends on its binding to G??. Additional data show that WDR26 also controlled RACK1, a negative regulator, in binding G?? and inhibiting leukocyte migration. Collectively, these experiments identify WDR26 as a novel G??-binding protein that is required for the efficacy of G?? signaling and leukocyte migration.

SUBMITTER: Sun Z

PROVIDER: S-EPMC3243526 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration.

Sun Zhizeng Z Tang Xiaoyun X Lin Fang F Chen Songhai S

The Journal of biological chemistry 20111107 51

The Gβγ subunits of heterotrimeric G proteins transmit signals to control many cellular processes, including leukocyte migration. Gβγ signaling may regulate and be regulated by numerous signaling partners. Here, we reveal that WDR26, a member of the WD40 repeat protein family, directly bound free Gβγ in vitro, and formed a complex with endogenous Gβγ in Jurkat T cells stimulated by the chemokine SDF1α. Suppression of WDR26 by siRNAs selectively inhibited Gβγ-dependent phospholipase Cβ and PI3K a ...[more]

PMID: 22065575

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Dataset Information

The WD40 repeat protein WDR26 binds G?? and promotes G??-dependent signal transduction and leukocyte migration.

Publications

The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration.

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