Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

Project description:Trp-Asp (WD) repeat protein 68 (WDR68) is an evolutionarily conserved WD40 repeat protein that binds to several proteins, including dual specificity tyrosine phosphorylation-regulated protein kinase (DYRK1A), MAPK/ERK kinase kinase 1 (MEKK1), and Cullin4-damage-specific DNA-binding protein 1 (CUL4-DDB1). WDR68 affects multiple and diverse physiological functions, such as controlling anthocyanin synthesis in plants, tissue growth in insects, and craniofacial development in vertebrates. However, the biochemical basis and the regulatory mechanism of WDR68 activity remain largely unknown. To better understand the cellular function of WDR68, here we have isolated and identified cellular WDR68 binding partners using a phosphoproteomic approach. More than 200 cellular proteins with wide varieties of biochemical functions were identified as WDR68-binding protein candidates. Eight T-complex protein 1 (TCP1) subunits comprising the molecular chaperone TCP1 ring complex/chaperonin-containing TCP1 (TRiC/CCT) were identified as major WDR68-binding proteins, and phosphorylation sites in both WDR68 and TRiC/CCT were identified. Co-immunoprecipitation experiments confirmed the binding between TRiC/CCT and WDR68. Computer-aided structural analysis suggested that WDR68 forms a seven-bladed ?-propeller ring. Experiments with a series of deletion mutants in combination with the structural modeling showed that three of the seven ?-propeller blades of WDR68 are essential and sufficient for TRiC/CCT binding. Knockdown of cellular TRiC/CCT by siRNA caused an abnormal WDR68 structure and led to reduction of its DYRK1A-binding activity. Concomitantly, nuclear accumulation of WDR68 was suppressed by the knockdown of TRiC/CCT, and WDR68 formed cellular aggregates when overexpressed in the TRiC/CCT-deficient cells. Altogether, our results demonstrate that the molecular chaperone TRiC/CCT is essential for correct protein folding, DYRK1A binding, and nuclear accumulation of WDR68.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets