title: Tyrosine phosphorylation of RalGDS by c-Met receptor blocks its interaction with Ras.
abstract: RalGDS is a guanine nucleotide exchange factor that promotes the active GTP-bound form of Ral GTPases, RalA and RalB. GTP-bound Ras has the capacity to activate Ral GTPases at least in part by binding to the C-terminal Ras-binding domain (RBD) of RalGDS and directing the protein to Ral GTPases in the plasma membrane. In many cases, activation of Ral proteins complements other Ras effector pathways to carry out a cell function, but in others it opposes them. Moreover, in many cases activation of Ral proteins contributes to the oncogenic potential of Ras. However, in some cell types Ral proteins suppresses tumor formation, suggesting oncogenic stimuli that function through Ras may need to suppress Ral activation in order to transform cells. In this paper, we demonstrate a potential biochemical mechanism for such phenomena by showing that c-Met receptors promote the tyrosine phosphorylation of RalGDS at Y752 in its RBD, which blocks the binding of Ras to RalGDS.
authors: Department of Developmental, Molecular and Chemical Biology, Sackler School of Graduate Biomedical Sciences, Tufts Medical School, Boston, MA, USA. Electronic address: rlw008@ucsd.edu.
authors: Richard
authors: R
authors: Wong
authors: Department of Developmental, Molecular and Chemical Biology, Sackler School of Graduate Biomedical Sciences, Tufts Medical School, Boston, MA, USA. Electronic address: larry.feig@tufts.edu.
authors: Larry A
authors: LA
authors: Feig
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C097104:Rgl1 protein, mouse; D014443:Tyrosine; D019859:Proto-Oncogene Proteins c-met; D018631:ras Proteins
keywords: Ral; RalGDS; Ras; Tyrosine phosphorylation; c-Met