Galectin-1(L11A) Predicted from a Computed Galectin-1 Farnesyl-Binding Pocket Selectively Inhibits Ras-GTP

Barak Rotblat, Hagit Niv, Sabine André, Herbert Kaltner, Hans Joachim Gabius, Yoel Kloog

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Ras biological activity necessitates membrane anchorage that depends on the Ras farnesyl molety and is strengthened by Ras/galectin-1 interactions. We identified a hydrophobic pocket in galectin-1, analogous to the Cdc42 geranylgeranyl-binding cavity in RhoGDI, possessing homologous isoprenoid-binding residues, including the critical L11, whose RhoGDI L77 homologue changes dramatically on Cdc42 binding. By substituting L11A, we obtained a dominant interfering galectin-1 that possessed normal carbohydrate-binding capacity but inhibited H-Ras GTP-loading and extracellular signal-regulated kinase activation, dislodged H-Ras(G12V) from the cell membrane, and attenuated H-Ras(G12V) fibroblast transformation and PC12-cell neurite outgrowth. Thus, independently of carbohydrate binding, galectin-1 cooperates with Ras, whereas galectin-1(L11A) inhibits it.

Original languageEnglish
Pages (from-to)3112-3118
Number of pages7
JournalCancer Research
Volume64
Issue number9
DOIs
StatePublished - 1 May 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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