REGULATION OF CELL-ADHESION RECEPTORS BY TRANSFORMING GROWTH FACTOR-BETA - CONCOMITANT REGULATION OF INTEGRINS THAT SHARE A COMMON BETA-1-SUBUNIT

  • 5 January 1989
    • journal article
    • research article
    • Vol. 264  (1) , 380-388
Abstract
Cell adhesion to extracellular matrices is mediated by a set of heterodimeric cell surface receptors called integrins that might be the subject of regulation by growth and differentiation factors. We have examined the effect of transforming growth factor-.beta.1 (TGF-.beta.1) on the expression of the very late antigens of .alpha..beta.1 group of integrins in human cell lines. The six known members of this family share a common .beta.1 subunit but have distinct .alpha. subunits that confer selective affinity toward type I collagen, fibronectin, laminin, and other as yet unknown cell adhesion proteins. Using a panel of specific antibodies and cDNA probes, we show that in WI-38 lung fibroblasts TGF-.beta.1 elevates concomitantly the expression of .alpha.1, .alpha.2, .alpha.3, .alpha.5, and .beta.1 integrin subunits at the protein and/or mRNA level, their assembly into the corresponding .alpha..beta.1 complexes, and their exposure on the cell surface. The rate of synthesis of total .alpha. subunits relative to .beta.1 subunit is higher in TGF-.beta.1-treated cells than in control cells. The characteristically slow (t1/2 .apprx. 10 h) rate of .beta.1 conversion from precursor from to mature glycoprotein in untreated cells increases markedly (to t1/2 7s 3 h) in response to TGF-.beta.1. The results suggest that in WI-38 fibroblasts the .beta.1 subunit is synthesized in excess over .alpha. subunits, and assembly of .beta.1 subunits with rate-limiting .alpha. subunits is required for transit through the Golgi and exposure of .alpha..beta.1 complex on the cell surface. TGF-.beta.1 does not induced the synthesis of integrin subunits that are not expressed in unstimulated cells, such as .alpha.4 and .alpha.6 subunits in WI-38 fibroblasts. However, .alpha.4 and .alpha.6 subunits can be regulated by TGF-.beta. in those cells that express them. The results suggest that TGF-.beta. regulates the expression of individual integrin subunits by parallel but independent mechanisms. By modifying the balance of individual .alpha..beta.1 integrins, TGF-.beta.1 might modulate those aspects of cell migration, positioning, and development that are guided by adhesion to extracellular matrices.

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