AffiliationCell Signaling Group, Cancer Research UK Manchester Institute, The University of Manchester , Manchester M20 4BX
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AbstractGEFs play a critical role in regulating Rac1 signaling. They serve as signaling nodes converting upstream signals into downstream Rac1-driven cellular responses. Through associating with membrane-bound Rac1, GEFs facilitate the exchange of GDP for GTP, thereby activating Rac1. As a result, Rac1 undergoes conformational changes that mediate its interaction with downstream effectors, linking Rac1 to a multitude of physiological and pathological processes. Interestingly, at least 20 GEFs have been shown to activate Rac1, suggesting a more complex role of GEFs in regulating Rac1 signaling apart from promoting the exchange of GDP for GTP. Indeed, accumulating evidence implicates GEFs in directing the specificity of Rac1-driven signaling cascades, although the underlying mechanisms were poorly defined. Recently, through conducting a comparative study, we highlighted the role of two Rac-specific GEFs, Tiam1 and P-Rex1, in dictating the biological outcome downstream of Rac1. Importantly, further proteomic analysis uncovered a GEF activity-independent role of both GEFs in modulating the Rac1 interactome, which results in the stimulation of GEF-specific signaling cascades. Here, we provide an overview of our recent findings and discuss the role of GEFs as master regulators of Rac1 signaling with a particular focus on GEF-mediated modulation of cell migration following Rac1 activation.
CitationGEFs: Dual regulation of Rac1 signaling. 2016:0 Small GTPases
TypeMeetings and Proceedings
- Proteomic analysis of Rac1 signaling regulation by guanine nucleotide exchange factors.
- Authors: Marei H, Carpy A, Macek B, Malliri A
- Issue date: 2016 Aug 2
- The guanine nucleotide exchange factor Tiam1: a Janus-faced molecule in cellular signaling.
- Authors: Boissier P, Huynh-Do U
- Issue date: 2014 Mar
- Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration.
- Authors: Marei H, Carpy A, Woroniuk A, Vennin C, White G, Timpson P, Macek B, Malliri A
- Issue date: 2016 Feb 18
- Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors.
- Authors: Gao Y, Xing J, Streuli M, Leto TL, Zheng Y
- Issue date: 2001 Dec 14
- Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration.
- Authors: Bourguignon LY, Zhu H, Shao L, Chen YW
- Issue date: 2000 Jul 10