Activation of c-Ha-Ras by Nitric Oxide Modulates Survival Responsiveness in Neuronal PC12 Cells*

p21c-Ha-Ras (Ras) can be activated by the guanine nucleotide exchange factor mSOS1 or byS-nitrosylation of cysteine 118 via nitric oxide (NO). To determine whether these two Ras-activating mechanisms modulate distinct biological effects, a NO-nonresponsive Ras mutant (RasC118S) was stably expressed in the PC12 cells, a cell line that generates NO upon nerve growth factor treatment. We report here that RasC118S functions indistinguishably from wild type Ras in activating and maintaining the mSOS1- and Raf-1-dependent mitogen-activated protein kinase cascade necessary for neuronal differentiation. However, continuous (>5 days) exposure to nerve growth factor reveals that, in contrast to parental or wild-type Ras-overexpressing PC12 cells, RasC118S-expressing PC12 cells cannot sustain the basal interaction between Ras and phosphatidylinositol 3-kinase. This results in spontaneous apoptosis of these cells despite the presence of nerve growth factor and serum. Thus unique downstream effector interactions and biological outcomes can be differentially modulated by distinct modes of Ras activation.

• Publication year

  1999

• Venue

  Journal of Biological Chemistry

• Publication date

  1999-12-24

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.274.52.37315PMID 10601298
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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