title: SodC modulates ras and PKB signaling in Dictyostelium.
abstract: We have previously reported that the basal RasG activity is aberrantly high in cells lacking Superoxide dismutase C (SodC). Here we report that other Ras proteins such as RasC and RasD activities are not affected in sodC-cells and mutagenesis studies showed that the presence of the Cys118in the Ras proteins is essential for the superoxide-mediated activation of Ras proteins in Dictyostelium. In addition to the loss of SodC, lack of extracellular magnesium ions increased the level of intracellular superoxide and active RasG proteins. Aberrantly active Ras proteins in sodC-cells persistently localized at the plasma membrane, but those in wild type cells under magnesium deficient medium exhibited intracellular vesicular localization. Interestingly, the aberrantly activated Ras proteins in wild type cells were largely insulated from their normal downstream events such as Phosphatidylinositol-3,4,5-P3(PIP3) accumulation, Protein Kinase B (PKB) activation, and PKBs substrates phosphorylation. Intriguingly, however, aberrantly activated Ras proteins in sodC-cells were still engaged in signaling to their downstream targets, and thus excessive PKBs substrates phosphorylation persisted. In summary, we suggest that SodC and RasG proteins are essential part of a novel inhibitory mechanism that discourages oxidatively stressed cells from chemotaxis and thus inhibits the delivery of potentially damaged genome to the next generation.
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Castillo
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Biochemistry PhD Program, Florida International University, Miami, FL 33199, USA.
authors.forename: Mujataba
authors.initials: M
authors.lastname: Sharief
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.affiliation: Biochemistry PhD Program, Florida International University, Miami, FL 33199, USA. Electronic address: kiml@fiu.edu.
authors.forename: Lou W
authors.initials: LW
authors.lastname: Kim
mesh_terms: D004023:Dictyostelium / Q000201:enzymology* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; C424065:rasG protein, Dictyostelium; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt
keywords: PKB; Ras; Superoxide