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Ras oncogene directs expression of a differentially sialylated, functionally altered beta1 integrin

Eric Clinton Seales1, Gustavo Adolfo Jurado, Anuj Singhal

  • 1Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Oncogene
|October 17, 2003
PubMed

Insights

Variant N-glycosylation regulates beta1 integrins, impacting cell adhesion. Oncogenic ras alters beta1 integrin sialylation, affecting collagen binding, but not vitronectin binding. This highlights sialic acids

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Integrin cell adhesion receptors are crucial for cellular processes.
  • Understanding integrin regulation is vital for numerous biological functions.
  • N-glycosylation is a post-translational modification with regulatory roles.

Purpose of the Study:

  • To investigate the role of N-glycosylation, specifically sialylation, in integrin regulation.
  • To determine if variant sialylation affects beta1, beta3, or beta5 integrins.
  • To elucidate the mechanism by which ras signaling influences integrin sialylation and function.

Main Methods:

  • Utilized oncogenic and dominant-negative ras expression in HD3 colonocytes.
  • Analyzed alpha2-6 sialylation of beta1, beta3, and beta5 integrins using RT-PCR.
  • Assessed cell adhesion to collagen I and vitronectin.
  • Performed enzymatic removal of sialic acids and cell-free binding assays with purified integrins.

Main Results:

  • Oncogenic ras increased alpha2-6 sialylation of beta1 integrins; dominant-negative ras decreased it.
  • Beta3 and beta5 integrins showed no significant alpha2-6 sialylation irrespective of ras status.
  • Differential beta1 integrin sialylation altered adhesion to collagen I but not vitronectin.
  • Desialylated alpha1beta1 integrins exhibited reduced collagen-binding capability.

Conclusions:

  • Variant N-glycosylation, specifically alpha2-6 sialylation, is a key regulatory mechanism for beta1 integrins.
  • Ras signaling modulates beta1 integrin function through altered sialylation, impacting collagen binding.
  • Sialic acids play a causal role in regulating beta1 integrin-mediated cell adhesion.

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