Regulation of cell adhesion receptors by transforming growth factor-beta. Regulation of vitronectin receptor and LFA-1
Ignotz, Ronald A. ; Heino, Jyrki ; Massague, Joan
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Keywords
Antigens, Differentiation
Antigens, Surface
*Cell Adhesion
Cell Adhesion Molecules
Cell Line
Humans
Lymphocyte Function-Associated Antigen-1
Macromolecular Substances
Membrane Glycoproteins
Mice
RNA, Messenger
Receptors, Immunologic
Receptors, Vitronectin
Transforming Growth Factors
Life Sciences
Medicine and Health Sciences
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Abstract
We have examined the ability of transforming growth factor-beta 1 (TGF-beta 1) to regulate the expression of members of the alpha beta 2 and alpha beta 3 families of integrins. TGF-beta 1 elevates the expression of vitronectin receptors (alpha v beta 3 integrin) in all cells examined including WI-38 human lung fibroblasts, 3T3-L1 mouse fibroblasts, and MG-63 human osteogenic sarcoma cells. TGF-beta 1 action increases the level of mRNA and the synthesis of vitronectin receptor subunits with t1/2 o 3-4 h and 6 h, respectively. TGF-beta 1 up-regulates expression of the intercellular adhesion receptor, LFA-1 (alpha L beta 2), in THP-1 human monocytic leukemia cells by increasing the synthesis of alpha L subunit but not beta 2 subunit. The increase in alpha L synthesis and assembly into LFA-1 complexes induced by TGF-beta 1 occurs in parallel with elevated fibronectin receptor synthesis in THP-1 cells. These responses to TGF-beta 1 are lost upon phorbol ester-induced differentiation of THP-1 cells into the macrophage phenotype. The results suggest a role of TGF-beta in the regulation of cell-matrix interactions mediated by vitronectin receptors and cell-cell interactions mediated by LFA-1 in the immune system.
Source
J Biol Chem. 1989 Jan 5;264(1):389-92.