title: The RalGEF/Ral pathway: evaluating an intervention opportunity for Ras cancers.
abstract: Recognition that Ral guanine nucleotide exchange factors (RalGEFs) are direct Ras effectors and that Ral G-protein activation is a direct consequence of Ras activation has spurred focused efforts to establish the contribution of RalGEF/Ral signaling to oncogenic transformation. Here, we provide a broad-strokes overview of the mechanistic organization of the RalGEF/Ral signaling network, evaluate the evidence for participation of this network in tumorigenic regulatory milieus, consider targeting strategies, and discuss the challenges to and opportunities for clinical development of these targeting strategies.
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cooper
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Bodemann
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, USA. Electronic address: michael.white@utsouthwestern.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: White
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D020725:ral GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D020726:ral Guanine Nucleotide Exchange Factor / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D020726:ral Guanine Nucleotide Exchange Factor; D020725:ral GTP-Binding Proteins
keywords: Cancer; Exo84; Exocyst; K-Ras; RALBP1; RalA; RalB; Sec5; TBK1; ULK1; mTORC1