PMID- 2491849
OWN - NLM
STAT- MEDLINE
DCOM- 19890207
LR  - 20210318
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 264
IP  - 1
DP  - 1989 Jan 5
TI  - Regulation of cell adhesion receptors by transforming growth factor-beta. 
      Concomitant regulation of integrins that share a common beta 1 subunit.
PG  - 380-8
AB  - 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 or 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 approximately 10 h) rate of beta 1 conversion from 
      precursor form to mature glycoprotein in untreated cells increases markedly (to 
      t1/2 approximately 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 induce 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.
FAU - Heino, J
AU  - Heino J
AD  - Department of Biochemistry, University of Massachusetts Medical School, Worcester 
      01655.
FAU - Ignotz, R A
AU  - Ignotz RA
FAU - Hemler, M E
AU  - Hemler ME
FAU - Crouse, C
AU  - Crouse C
FAU - Massague, J
AU  - Massague J
LA  - eng
GR  - CA39240/CA/NCI NIH HHS/United States
GR  - CA42368/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, Surface)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 76057-06-2 (Transforming Growth Factors)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
RN  - EC 3.2.1.96 (Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase)
SB  - IM
MH  - Acetylglucosaminidase
MH  - Antigens, Surface/*genetics
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Adhesion/*drug effects
MH  - Cell Adhesion Molecules
MH  - Cell Line
MH  - Humans
MH  - Macromolecular Substances
MH  - Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
MH  - Membrane Glycoproteins/biosynthesis/*genetics
MH  - Nucleic Acid Hybridization
MH  - RNA, Messenger/drug effects/genetics
MH  - Transforming Growth Factors/*pharmacology
EDAT- 1989/01/05 00:00
MHDA- 1989/01/05 00:01
CRDT- 1989/01/05 00:00
PHST- 1989/01/05 00:00 [pubmed]
PHST- 1989/01/05 00:01 [medline]
PHST- 1989/01/05 00:00 [entrez]
AID - S0021-9258(17)31269-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1989 Jan 5;264(1):380-8.