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dc.date.accessioned2018-07-10T13:22:16Z
dc.date.issued2013-04
dc.identifierhttp://publications.icr.ac.uk/12472/
dc.identifier.citationCELL, 2013, 153 (3), pp. 640 - 653
dc.identifier.issn0092-8674
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2018
dc.description.abstractSignaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP- bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3-binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins.
dc.format.extent640 - 653
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectrho-family cell-migration caax motif binding ras organization gtpases kinase rap1a cytoskeleton
dc.title14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins
dc.typeJournal Article
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2013-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCELL
pubs.issue3
pubs.notesISI Document Delivery No.: 132JK Times Cited: 0 Cited Reference Count: 37 Riou, Philippe Kjaer, Svend Garg, Ritu Purkiss, Andrew George, Roger Cain, Robert J. Bineva, Ganka Reymond, Nicolas McColl, Brad Thompson, Andrew J. O'Reilly, Nicola McDonald, Neil Q. Parker, Peter J. Ridley, Anne J. BBSRC; MRC; King's College London Wellcome Trust VIP Award; Cancer Research UK; King's College London BHF Centre of Excellence; CJ Martin fellowship We thank Michael Yaffe (MIT) for communicating the interaction between 14-3-3 epsilon and Rnd3, providing 14-3-3 constructs, and discussions; Steen Hansen for the p190RhoGAP-B construct; Steve Lynham (Centre for Excellence in Mass Spectrometry, King's College London) for expert mass spectrometry assistance; Gavin Kelly (Cancer Research UK London Research Laboratories) for help with statistical analysis; and Jeroen Claus for designing the graphical abstract. We are grateful to members of the Ridley laboratory for helpful discussions. This work was supported by the BBSRC, MRC, a King's College London Wellcome Trust VIP Award, Cancer Research UK, and the King's College London BHF Centre of Excellence. B.M. was supported by a CJ Martin fellowship. Cell press Cambridge
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume153
pubs.embargo.termsNot known
dc.contributor.icrauthorThompson, Andrewen


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