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Steps in integrin beta1-chain glycosylation mediated by TGFbeta1 signaling through Ras

S L Bellis1, E Newman, E A Friedman

  • 1Department of Pathology, State University of New York Health Science Center, Syracuse, New York 13210, USA.

Journal of Cellular Physiology
|August 24, 1999
PubMed

Insights

Transforming growth factor beta (TGFbeta) activates Ras, a key mediator in integrin beta1-chain maturation. Ras signaling is crucial for TGFbeta1-induced conversion of beta1 integrin precursors into mature cell surface forms.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ras activation by transforming growth factor beta (TGFbeta) is observed in multiple cell types, but its functional outcomes remain largely uncharacterized.
  • Integrins are crucial cell surface receptors involved in cell adhesion and signaling, with their maturation process being vital for proper function.

Purpose of the Study:

  • To elucidate the biological consequences of Ras activation by TGFbeta, specifically its role in integrin beta1-chain maturation.
  • To investigate the mechanism by which TGFbeta1 influences the conversion of beta1 integrin precursors to their mature form.

Main Methods:

  • Utilized HD3 colon epithelial cells, known for high integrin alpha2beta1 levels and TGFbeta1 autocrine regulation.
  • Employed dominant-negative Ras (N17Ras) expression in HD3 cell clones to inhibit Ras signaling.
  • Applied antisense oligonucleotides targeting the rasS17N mutation to assess its effect on aberrant glycosylation.

Main Results:

  • Ras mediates two key stages of integrin beta1-chain maturation: core peptide glycosylation (TGFbeta1-independent) and precursor conversion to mature form (TGFbeta1-dependent).
  • Inhibition of Ras signaling via N17Ras expression led to abnormal beta1 integrin glycosylation, reduced cell surface expression, and impaired cell binding to collagen and laminin.
  • TGFbeta1-mediated conversion of the beta1 integrin precursor to the mature 130-kD isoform was dependent on Ras activation, occurring within the Golgi apparatus.

Conclusions:

  • TGFbeta1 modulates integrin beta1-chain maturation through the activation of Ras proteins.
  • Ras signaling is essential for the TGFbeta1-induced maturation of beta1 integrins, impacting cell adhesion and extracellular matrix interactions.
  • The findings reveal a novel regulatory pathway where TGFbeta1-activated Ras controls integrin functional maturation.

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