Galpha16 activates Ras by forming a complex with tetratricopeptide repeat 1 (TPR1) and Son of Sevenless (SOS)

Cellular Signalling
Andrew M F LiuYung H Wong

Abstract

Many G protein-coupled receptors (GPCRs) are known to modulate cell growth and differentiation by stimulating the extracellular signal-regulated protein kinases (ERKs). In growth factor signaling, ERKs are typically stimulated through an elaborate network of modules consisting of adaptors, protein kinases, and the small GTPase Ras. The mechanism by which G protein signals tap into the ERK signaling pathway has thus far remain elusive. Members of the Gq family of G proteins, in particular Galpha16, have been shown to associate with tetratricopeptide repeat 1 (TPR1), an adaptor protein which preferentially binds to Ras. Here, we examined if TPR1 is indeed the missing link between Galpha16 signaling and Ras activation. Expression of Galpha16QL, a constitutively active mutant of Galpha16, in HEK 293 cells led to the formation of GTP-bound Ras and the subsequent phosphorylation of ERK. Likewise, stimulation of endogenou G16-coupled CCR1 chemokine receptors produced the same responses in human erythroleukemia cells. siRNA-mediated knockdown of TPR1 or expression of a dominant negative mutant of TPR1 effectively abolished the ability of Galpha16QL to induce Ras activation in HEK 293 cells. In contrast, these manipulations had no inhib...Continue Reading

References

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Citations

May 29, 2013·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Agatino BattagliaJohn C Carey
Aug 21, 2013·Cell Communication and Signaling : CCS·Hao ZuoYung H Wong
Jun 20, 2012·Journal of Cellular Biochemistry·Dawna H T KwanYung H Wong
Sep 18, 2015·BMC Structural Biology·Dawna H T KwanYung H Wong
Jan 4, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jun YanJiping Tang
Nov 6, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maggie M K LeeYung H Wong
Nov 3, 2011·Molecular and Cellular Biochemistry·Angel K C IpYung H Wong
Jul 23, 2021·Scientific Reports·Giulio InnamoratiClaudio Bassi

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