WD40-repeat proteins control the flow of Gβγ signaling for directional cell migration

Runne, Caitlin; Chen, Songhai

doi:10.4161/cam.22940

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…Once on the membrane, WDR26 binds to G␤␥, thereby bringing PLC␤2 in close proximity to G␤␥ for interaction and activation. Given that WDR26 is ubiquitously expressed and is required for the efficient activation of other G␤␥ effectors such as PI3K␥ (16), such a mechanism of regulation by WDR26 may extend beyond PLC␤2 (32). In addition to PLC␤2, G␤␥ can also stimulate PLC␤3.…”

Section: Discussionmentioning

confidence: 99%

WDR26 Functions as a Scaffolding Protein to Promote Gβγ-mediated Phospholipase C β2 (PLCβ2) Activation in Leukocytes

Sun¹,

Smrcka

Chen

2013

Journal of Biological Chemistry

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Background: It remains unclear how G␤␥ regulates diverse effectors in cells. Results: WDR26 exists in oligomers. It simultaneously binds both G␤␥ and PLC␤2 to enhance PLC␤2 membrane translocation and activation by G␤␥ in leukocytes. Conclusion: WDR26 functions as a scaffolding protein to promote G␤␥-mediated PLC␤2 activation. Significance: These findings uncover a novel mechanism of regulating G␤␥ signaling through a scaffolding protein.

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Section: Discussionmentioning

confidence: 99%

WDR26 Functions as a Scaffolding Protein to Promote Gβγ-mediated Phospholipase C β2 (PLCβ2) Activation in Leukocytes

Sun¹,

Smrcka

Chen

2013

Journal of Biological Chemistry

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“…For example, binding of chemoattractants to G protein-coupled receptors on Jurkat cells induces the association of RACK1 with Gβγ subunits and recruitment of the complex to the leading edge, where it inhibits chemotaxis. RACK1 is thought to negatively regulate migration by preventing Gβγ stimulation of phosphoinositide 3-kinases and phospholipase C. 35,36 Thus, although RACK1 clearly plays a role in finetuning the events that control cell adhesion and motility, whether RACK1 enhances or inhibits these processes seems to be cell, context, or stimulus dependent.…”

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confidence: 99%

RACK1 Function in Cell Motility and Protein Synthesis

et al. 2013

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The receptor for activated C kinase 1 (RACK1) serves as an adaptor for a number of proteins along the MAPK, protein kinase C, and Src signaling pathways. The abundance and near ubiquitous expression of RACK1 reflect its role in coordinating signaling molecules for many critical biological processes, from mRNA translation to cell motility to cell survival and death. Complete deficiency of Rack1 is embryonic lethal, but the recent development of genetic Rack1 hypomorphic mice has highlighted the central role that RACK1 plays in cell movement and protein synthesis. This review focuses on the importance of RACK1 in these processes and places the recent work in the larger context of understanding RACK1 function.

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“…Conversely, WD40-repeat containing protein 26 (WDR26) might act as a positive regulator of Gβγ signaling functioning as a scaffold that recruits and translocates Gβγ effectors, suppression of WDR26 in HL60 cells resulted in loss of directionality and cell migration speed. Moreover, WDR26 suppression blocks RACK1 interaction with Gβγ, indicating that RACK1 functions downstream of WDR26 [ 76 ].…”

Section: Regulation Of Gpcrs and Heterotrimeric G Proteins During mentioning

confidence: 99%

Function and Regulation of Heterotrimeric G Proteins during Chemotaxis

Kamp¹,

Liu²,

Kortholt³

2016

IJMS

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Chemotaxis, or directional movement towards an extracellular gradient of chemicals, is necessary for processes as diverse as finding nutrients, the immune response, metastasis and wound healing. Activation of G-protein coupled receptors (GPCRs) is at the very base of the chemotactic signaling pathway. Chemotaxis starts with binding of the chemoattractant to GPCRs at the cell-surface, which finally leads to major changes in the cytoskeleton and directional cell movement towards the chemoattractant. Many chemotaxis pathways that are directly regulated by Gβγ have been identified and studied extensively; however, whether Gα is just a handle that regulates the release of Gβγ or whether Gα has its own set of distinct chemotactic effectors, is only beginning to be understood. In this review, we will discuss the different levels of regulation in GPCR signaling and the downstream pathways that are essential for proper chemotaxis.

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WD40-repeat proteins control the flow of Gβγ signaling for directional cell migration

Cited by 11 publications

References 37 publications

WDR26 Functions as a Scaffolding Protein to Promote Gβγ-mediated Phospholipase C β2 (PLCβ2) Activation in Leukocytes

WDR26 Functions as a Scaffolding Protein to Promote Gβγ-mediated Phospholipase C β2 (PLCβ2) Activation in Leukocytes

RACK1 Function in Cell Motility and Protein Synthesis

Function and Regulation of Heterotrimeric G Proteins during Chemotaxis

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