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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
Summary
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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