Altered localization of h-ras in caveolin-1-null cells is palmitoylation-independent

Joanne Baran, Dorothy I. Mundy, Amit Vasanji, Marie Odile Parat

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Caveolin-1 is a palmitoylated protein involved in the formation of plasma membrane subdomains termed caveolae, intracellular cholesterol transport, and assembly and regulation of signaling molecules in caveolae. Caveolin-1 interacts via a consensus binding motif with several signaling proteins, including H-Ras. Ras oncogene products function as molecular switches in several signal transduction pathways regulating cell growth and differentiation. Post-translational modifications, including palmitoylation, are critical for the membrane targeting and function of H-Ras. Subcellular localization regulates the signaling pathways engaged by H-Ras activation. We show here that H-Ras is localized at the plasma membrane in caveolin-1-expressing cells but not in caveolin-1-deficient cells. Since palmitoylation is required for trafficking of H-Ras from the endomembrane system to the plasma membrane, we tested whether the altered localization of H-Ras in caveolin-1-null cells is due to decreased H-Ras palmitoylation. Although the palmitoylation profiles of cultured embryo fibroblasts isolated from wild type and caveolin-1 gene-disrupted mice differed, suggesting that caveolin-1, or caveolae, play a role in the palmitate incorporation of a subset of palmitoylated proteins, the palmitoylation of H-Ras was not decreased in caveolin-1-null cells. We conclude that the altered localization of H-Ras in caveolin-1-deficient cells is palmitoylation-independent. This article shows two important new mechanisms by which loss of caveolin-1 expression may perturb intracellular signaling, namely the mislocalization of signaling proteins and alterations in protein palmitoylation.

Original languageEnglish (US)
Pages (from-to)195-204
Number of pages10
JournalJournal of Cell Communication and Signaling
Volume1
Issue number3-4
DOIs
StatePublished - 2007

Fingerprint

Lipoylation
Caveolin 1
Null Lymphocytes
Caveolae
Cell membranes
Cell Membrane
Proteins
Signal transduction
ras Genes
Palmitates
Oncogene Proteins
Cell growth
Fibroblasts
Post Translational Protein Processing
Cell Differentiation
Signal Transduction
Embryonic Structures
Genes
Chemical activation
Cholesterol

Keywords

  • Palmitate
  • Post translational modification

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Altered localization of h-ras in caveolin-1-null cells is palmitoylation-independent. / Baran, Joanne; Mundy, Dorothy I.; Vasanji, Amit; Parat, Marie Odile.

In: Journal of Cell Communication and Signaling, Vol. 1, No. 3-4, 2007, p. 195-204.

Research output: Contribution to journalArticle

Baran, Joanne ; Mundy, Dorothy I. ; Vasanji, Amit ; Parat, Marie Odile. / Altered localization of h-ras in caveolin-1-null cells is palmitoylation-independent. In: Journal of Cell Communication and Signaling. 2007 ; Vol. 1, No. 3-4. pp. 195-204.
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