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[摘要]：The G beta gamma subunits of heterotrimeric G proteins transmit signals to control many cellular processes, including leukocyte migration. G beta gamma 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 beta gamma in vitro, and formed a complex with endogenous G beta gamma in Jurkat T cells stimulated by the chemokine SDF1 alpha. Suppression of WDR26 by siRNAs selectively inhibited G beta gamma-dependent phospholipase C beta 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 beta gamma interaction via expression of a WDR26 deletion mutant impaired G beta gamma signaling and Jurkat T cell migration, indicating that the function of WDR26 depends on its binding to G beta gamma. Additional data show that WDR26 also controlled RACK1, a negative regulator, in binding G beta gamma and inhibiting leukocyte migration. Collectively, these experiments identify WDR26 as a novel G beta gamma-binding protein that is required for the efficacy of G beta gamma signaling and leukocyte migration. |
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