GEFs: Dual regulation of Rac1 signaling.
GEFs 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, there are at least 20 GEFs involved in Rac1 activation, 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 2 Rac-specific GEFs, Tiam1 and P-Rex1, in dictating the biological outcome downstream of Rac1. Importantly, further proteomic analysis uncovered a GEF activity-independent function for 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.
a Cell Signaling Group, Cancer Research UK Manchester Institute , The University of Manchester , Manchester , UK.
Hadir
H
Marei
a Cell Signaling Group, Cancer Research UK Manchester Institute , The University of Manchester , Manchester , UK.
Angeliki
A
Malliri
D000818:Animals; D002465:Cell Movement; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D020830:rac1 GTP-Binding Protein
IQGAP1, MLC; NMMIIA; PRex-1; FLII; Rac1; Tiam1; cell contraction; cell invasion; cell migration; guanine nucleotide exchange factors (GEFs)