Regulation of cell adhesion receptors by transforming growth factor-beta. Regulation of vitronectin receptor and LFA-1.
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.
Ignotz
R A
RA
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
Heino
J
J
Massagué
J
J
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002460:Cell Line; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*; D019030:Receptors, Vitronectin; D015291:Transforming Growth Factors / Q000494:pharmacology*
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019030:Receptors, Vitronectin; D015291:Transforming Growth Factors