Intercellular Adhesion Molecule-1 (ICAM-1) Gene Expression in Human T Cells Is Regulated by Phosphotyrosyl Phosphatase Activity

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in adhesion phenomena involved in the immune response. The strength of adhesion has been shown to be modulated by changes in ICAM-1 gene expression. In T cells, signaling pathways are intimately regulated by an equilibrium between protein-tyrosine kinases and protein tyrosine phosphatases (PTP). The use of bis-peroxovanadium (bpV) compounds, a class of potent PTP inhibitors, enabled us to investigate the involvement of phosphotyrosyl phosphatases in the regulation of ICAM-1 gene expression in human T cells. Here, we demonstrate for the first time that inhibition of PTP results in an increase of ICAM-1 surface expression on both human T lymphoid and primary mononuclear cells. The crucial role played by the NF-κB-, Ets-, and pIγRE-binding sites in bpV[pic]-mediated activation of ICAM-1 was demonstrated using various 5′ deletion and site-specific mutants of the ICAM-1 gene promoter driving the luciferase reporter gene. Co-transfection experiments withtrans-dominant mutants and electrophoretic mobility shift assays confirmed the importance of constitutive and inducible transcription factors that bind to specific responsive elements in bpV-dependent up-regulation of ICAM-1 surface expression. Altogether, these observations suggest that expression of ICAM-1 in human T cells is regulated by phosphotyrosyl phosphatase activity through NF-κB-, Ets-, and STAT-1-dependent signaling pathways. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in adhesion phenomena involved in the immune response. The strength of adhesion has been shown to be modulated by changes in ICAM-1 gene expression. In T cells, signaling pathways are intimately regulated by an equilibrium between protein-tyrosine kinases and protein tyrosine phosphatases (PTP). The use of bis-peroxovanadium (bpV) compounds, a class of potent PTP inhibitors, enabled us to investigate the involvement of phosphotyrosyl phosphatases in the regulation of ICAM-1 gene expression in human T cells. Here, we demonstrate for the first time that inhibition of PTP results in an increase of ICAM-1 surface expression on both human T lymphoid and primary mononuclear cells. The crucial role played by the NF-κB-, Ets-, and pIγRE-binding sites in bpV[pic]-mediated activation of ICAM-1 was demonstrated using various 5′ deletion and site-specific mutants of the ICAM-1 gene promoter driving the luciferase reporter gene. Co-transfection experiments withtrans-dominant mutants and electrophoretic mobility shift assays confirmed the importance of constitutive and inducible transcription factors that bind to specific responsive elements in bpV-dependent up-regulation of ICAM-1 surface expression. Altogether, these observations suggest that expression of ICAM-1 in human T cells is regulated by phosphotyrosyl phosphatase activity through NF-κB-, Ets-, and STAT-1-dependent signaling pathways. intercellular adhesion molecule-1 protein tyrosine phosphatases bis-peroxovanadium bis-peroxovanadium compound carrying the picolinic acid as an auxillary ligand palindromic interferon-γ-responsive element signal transducers and activators of transcription phorbol 12-myristate 13-acetate ionomycin fetal bovine serum peripheral blood mononuclear cells phosphate-buffered saline wild type double-stranded DNA mutant interleukin interferon tumor necrosis factor-α base pair Intercellular adhesion molecule-1 (ICAM-1)1 is an inducible cell surface glycoprotein belonging to the immunoglobulin supergene family that shows a molecular mass ranging from 76 to 114 kDa depending on the degree of glycosylation. Its cognate ligands include the membrane-bound integrin receptor LFA-1, Mac-1 on leukocytes, the soluble molecule fibrinogen, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes (1Marlin S.D. Springer T.A. Cell. 1987; 51: 813-819Abstract Full Text PDF PubMed Scopus (1393) Google Scholar, 2Staunton D.E. Merluzzi V.J. Rothlein R. Barton R. Marlin S.D. Springer T.A. Cell. 1989; 56: 849-853Abstract Full Text PDF PubMed Scopus (607) Google Scholar, 3Greve J.M. Davis G. Meyer A.M. Forte C.P. Yost S.C. Marlor C.W. Kamarck M.E. McClelland A. Cell. 1989; 56: 839-847Abstract Full Text PDF PubMed Scopus (857) Google Scholar, 4Berendt A.R. Simmons D.L. Tansey J. Newbold C.I. Marsh K. Nature. 1989; 341: 57-59Crossref PubMed Scopus (570) Google Scholar, 5Diamond M.S. Staunton D.E. de Fougerolles A.R. Stacker S.A. Garcia-Aguilar J. Hibbs M.L. Springer T.A. J. Cell Biol. 1990; 111: 3129-3139Crossref PubMed Scopus (769) Google Scholar). Within the immune system, ICAM-1 is expressed on cells of the monocyte-macrophage lineage, B lymphocytes, plasma cells, and on both memory and activated T lymphocytes. The association between ICAM-1 and the activated form of the LFA-1 counter-receptor has many important roles in adhesion phenomena involved in the immune system. Its basic function is the induction of a specific and reversible cell-cell adhesion that enables intercellular communication, T cell-mediated defense mechanism, and inflammatory response. In addition, ICAM-1 is also involved in leukocyte-endothelial cell interaction, cell differentiation, and in many pathological complications such as acquired immunodeficiency syndrome, malignancies of both myeloid and lymphoid origin, and allergic asthma (6Noraz N. Verrier B. Fraisier C. Desgranges C. AIDS Res. Hum. Retroviruses. 1995; 11: 145-154Crossref PubMed Scopus (23) Google Scholar, 7van de Stolpe A. van der Saag P.T. J. Mol. Med. 1996; 74: 13-33Crossref PubMed Scopus (648) Google Scholar, 8Roebuck K.A. Finnegan A. J. Leukocyte Biol. 1999; 66: 876-888Crossref PubMed Scopus (462) Google Scholar). In a normal immune response, the initial contact between T lymphocytes and antigen presenting cells is made possible through an interaction between adhesion molecules such as ICAM-1 and LFA-1 expressed on the surface of both T lymphocytes and antigen presenting cells. This interaction leads to the association between the T cell receptor-CD3 complex and antigenic peptides in the context of major histocompatibility complex class I and II molecules. If the latter interaction occurs, T cell receptor-CD3 receptors and major histocompatibility complex molecules transmit activation signals in both cell partners. One of the first reactions following such activation is an increase of adhesion strength stabilizing the association between T cells and antigen presenting cells. Additional links occur between other molecules expressed on both cell surfaces that are required for completing adhesion and cell signaling and consequently determining the following response. It ensues that a dysfunction in ICAM-1 gene expression results in an immunological impairment or a physiopathological situation (7van de Stolpe A. van der Saag P.T. J. Mol. Med. 1996; 74: 13-33Crossref PubMed Scopus (648) Google Scholar,8Roebuck K.A. Finnegan A. J. Leukocyte Biol. 1999; 66: 876-888Crossref PubMed Scopus (462) Google Scholar). The regulation of ICAM-1 gene expression occurs primarily at the level of transcription and is cell type-specific. This phenomenon involves different signaling pathways and several enhancer elements such as palindromic interferon-γ-responsive element (pIγRE), NF-κB, Ets, C/EBP, AP-1-like, Sp1, and retinoic acid response elements (7van de Stolpe A. van der Saag P.T. J. Mol. Med. 1996; 74: 13-33Crossref PubMed Scopus (648) Google Scholar, 8Roebuck K.A. Finnegan A. J. Leukocyte Biol. 1999; 66: 876-888Crossref PubMed Scopus (462) Google Scholar, 9Stratowa C. Audette M. Immunobiology. 1995; 193: 293-304Crossref PubMed Scopus (66) Google Scholar). These numerous enhancer elements contained in theICAM-1 promoter suggest a complex regulation that is still ill-defined in human T cells. In various cell types, signal transducers and activators of transcription (STAT) factors, and more specifically STAT-1 and STAT-3, can bind the ICAM-1 promoter pIγRE and are strongly involved in ICAM-1 gene expression (10Coccia E.M. Del Russo N.D. Stellacci E. Testa U. Marziali G. Battistini A. Int. Immunol. 1999; 11: 1075-1083Crossref PubMed Scopus (59) Google Scholar, 11Song S. Ling-Hu H. Roebuck K.A. Rabbi M.F. Donnelly R.P. Finnegan A. Blood. 1997; 89: 4461-4469Crossref PubMed Google Scholar, 12Sampath D. Castro M. Look D.C. Holtzmann M.J. J. Clin. Invest. 1999; 103: 1353-1361Crossref PubMed Scopus (195) Google Scholar, 13Li W. Nagineni C.N. Hooks J.J. Chepelinsky A.B. Egwuagu C.E. Invest. Ophthalmol. Vis. Sci. 1999; 40: 976-982PubMed Google Scholar, 14Lee S.J. Park J.Y. Hou J. Benveniste E.N. Glia. 1999; 25: 21-32Crossref PubMed Scopus (36) Google Scholar, 15Cantwell C.A. Sterneck E. Johnson P.F. Mol. Cell. Biol. 1998; 18: 2108-2117Crossref PubMed Google Scholar, 16Wu A.J. Chen Z.J. Kan E.C. Baum B.J. J. Cell. Physiol. 1997; 173: 110-114Crossref PubMed Scopus (18) Google Scholar, 17Duff J.L. Quinlan K.L. Paxton L.L. Naik S.M. Caughman J. Invest. 1997; Full Text PDF PubMed Scopus Google Scholar, S.M. N. Quinlan K.L. Paxton L.L. Caughman J. Biol. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, der E. D. Blood. 1995; PubMed Google Scholar). has also been to a role gene regulation and can ICAM-1 expression in several cell J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, N. J. Biol. Full Text PDF PubMed Google Scholar, A. Johnson PubMed Scopus Google Scholar, J. Sci. U. S. A. PubMed Scopus Google Scholar, de Stolpe A. E. Johnson van der Saag P.T. J. Biol. Full Text PDF PubMed Google Scholar, N. B. C. J. Audette M. Cell 1997; Google Scholar). and pathways been shown to be modulated by that to the In to and NF-κB, the gene family of factors is also involved in the regulation of ICAM-1 expression K.A. A. K. A.B. J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Audette M. H. S. 1998; PubMed Scopus Google Scholar). The of of by involves regulation at different specific by the in response to signals B. J. A. Sci. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). In T cells, the expression of many is regulated by an equilibrium between of the protein-tyrosine kinases and protein tyrosine phosphatases (PTP). The role of protein-tyrosine kinases in T cell gene expression has been Immunol. 1999; PubMed Scopus Google Scholar). the role of PTP in T cell signaling and T cell A. Immunol. PubMed Scopus Google Scholar, S. M. 1998; Scholar, M. Cell Biol. 1996; PubMed Scopus Google Scholar, Cell Biol. 1997; PubMed Scopus Google Scholar, Immunol. 1997; PubMed Scopus Google Scholar, A. Cell. Full Text PDF PubMed Scopus Google the involvement of PTP in the regulation of ICAM-1 gene expression in T cells is is the that the PTP can induction of ICAM-1 expression of STAT-1 in human J.L. Quinlan K.L. Paxton L.L. Naik S.M. Caughman J. Invest. 1997; Full Text PDF PubMed Scopus Google Scholar). and phosphatase inhibitors, an of both and cells J. Res. 1996; PubMed Scopus Google Scholar). the to been Altogether, these suggest that both PTP and phosphatases are involved in ICAM-1 expression. The primary of the was to investigate the role of PTP in the regulation of ICAM-1 gene expression in human T cells. that of primary human peripheral blood mononuclear cells and the human T cell and the bis-peroxovanadium compound a of results in the induction of ICAM-1 surface expression. experiments that NF-κB, Ets, and pIγRE-binding sites are important in bpV[pic]-mediated up-regulation of ICAM-1 expression. These results suggest that ICAM-1 is regulated in human T cells by PTP 12-myristate 13-acetate and ionomycin from and was use in The compound was as R. D. G. A. J. Biol. Full Text PDF PubMed Google Scholar). was in an and and an ligand acid in in to the for of was by and of in phosphate-buffered at The lymphoid T cell was from the cells in fetal bovine serum in a The human T cell van de R. Sci. U. S. A. 1990; PubMed Scopus (36) Google and the human T cell by the AIDS and of of and in in the of human for blood mononuclear cells from by and in in the of and human for at cells in for to or The following was through the AIDS and human from S. J. PubMed Scopus Google Scholar). Cell surface expression of ICAM-1 was by as cells, and in phosphate-buffered saline in of to was of and for on and in of and for on and in in by of the ICAM-1 element and mutants in these experiments are from the luciferase gene. and by and and by de and from N. the Rothlein the R. M.L. Marlin S.D. Springer T.A. J. Immunol. Google Scholar). The has been J. Mol. Cell. Biol. 1996; PubMed Google from W. C. The The DNA was from the by deletion of the for cells first in and and in of of the and The was for at cells at a of using of at cells in and at for cells at a of cells in In cells or or in a of for a of for or for and and luciferase activity was a cells or for different at or and of cells the various was by the of and to the Res. PubMed Scopus Google Scholar). In cells in of and on of was The was for and for at The was and the cell was in of B and at for by at for at and the was at mobility shift was of by the a protein for at in of of of bovine serum of double-stranded DNA DNA was and in a This was for at and the was of The was and through a The as or as contained the the the the pIγRE the sites or the sites of the ICAM-1 from DNA by in and The and assays by a of or NF-κB, or the assays by of of specific in the of the of the for at that tyrosine are crucial in the regulation of numerous we the of the on ICAM-1 protein expression in the human T cell and also in primary cells In of cells the a or and the of cells as as the of the of molecules cell shown on a by the use of an specific for ICAM-1 in and ICAM-1 is expressed on both cells and in a increase ICAM-1 expression on cells, a induction of ICAM-1 protein was by these in primary cells. the tyrosine in a up-regulation of ICAM-1 protein expression on T cells of PTP by the specific also leads to a induction of ICAM-1 expression in Cell was by and as by in assays These the first that are in ICAM-1 gene expression in human T cells. It be that we made observations using human T cell and an T cell cell from the blood cells of a T cell B and This of experiments that the bpV[pic]-mediated induction of ICAM-1 gene expression is an is in several human T cell It is that ICAM-1 gene expression is primarily regulated at the In an to the of on ICAM-1 a was using of PTP cells a reporter made of the luciferase gene of the cells the or for the increase of ICAM-1 promoter activity in cells was using of ranging from to of luciferase activity was at the be to cell experiments using at a of a PTP was in of shown in a increase in luciferase activity was of ranging from to these suggest that is a more potent promoter transcription the other PTP also to the time to and activation of ICAM-1 shown in was to be more potent to activation of ICAM-1 activation of luciferase activity was following the induction of ICAM-1 transcription was following of These time for the following of demonstrated that compound as a potent of ICAM-1 transcription in human T cells, we the the of the that to tyrosine This was using a of ICAM-1 reporter carrying or in the 5′ of the promoter mutants of specific transcription of these molecular was cells, and the luciferase of and cells the involvement of the transcription in activation promoter is a transcription complex that the regulated expression of enhancer the of as as for cell adhesion molecules ICAM-1 U. G. K. Cell Biol. PubMed Scopus Google Scholar). has been to a role in the cell and regulation of ICAM-1 (7van de Stolpe A. van der Saag P.T. J. Mol. Med. 1996; 74: 13-33Crossref PubMed Scopus (648) Google Scholar). that the of the has been demonstrated to be important for the induction of ICAM-1 transcription S. S. J. Immunol. 1997; PubMed Scopus Google S. C. U. N. Caughman K. J. Invest. 1995; Full Text PDF PubMed Scopus Google we and a of the ICAM-1 promoter a in the or for and for of ICAM-1 induction the reporter the ICAM-1 promoter of the in a in the induction in response to both and and and can be that the is a element for ICAM-1 induction in T cells is the observations suggest that can other transcription factors that are to bind to theICAM-1 promoter D. J. 1995; PubMed Scopus Google Scholar, S. van de Stolpe A. E. van der Saag Immunobiology. 1997; PubMed Scopus Google Scholar). to more the of in bpV-dependent activation of ICAM-1 cells and a for a of to on both and The protein by is in the and the complex to to the The of the to and activation of was by of cells and a made of sites for of the promoter on bpV[pic]-mediated reporter gene activity the of the was of the cells compound a in ICAM-1 promoter activity and more of reporter gene activity was following and These confirmed the role played by in promoter The ICAM-1 promoter also a more In an to the of both in the up-regulation of ICAM-1 transcription by the and sites of the ICAM-1 promoter and as for DNA mobility shift from and cells in these of or was at time an that is a B. R. N. G. M. R. M. J. Biol. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). in a complex was following both the tyrosine and and using the as a such complex be by or the was as a The complex was by the of a of complex was by a the of the the involved in complex of the and from and cells the of the complex and a a It is that the protein complex to the of theICAM-1 promoter is of both and These results that compound is of NF-κB, and such a is in and results that a in the or the use of a form of the the of the ICAM-1 promoter to to and that signal be involved as sites in the ICAM-1 promoter K.A. A. K. A.B. J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Audette M. H. S. 1998; PubMed Scopus Google Scholar). It be that the role of these transcription elements in human T cells to the regulation of theICAM-1 gene to be in a a by the first of the ICAM-1 promoter This of the ICAM-1 promoter sites and to the of in to the and and a cells also molecular at and or both cells or for and for level of and ICAM-1 induction was using and of theICAM-1 promoter carrying in or both sites the induction by was It be that induction of ICAM-1 transcription is by such these can function as the responsive of both and sites was and as a for mobility shift we that was a constitutive of in cells that was modulated by a or The complex was by of a of sites and by a signal was using a at the sites results from experiments and mobility shift assays demonstrated the importance of sites in bpV[pic]-mediated ICAM-1 gene the complex the is modulated by expression of transcription factors that bind to the sites in the ICAM-1 sites of the from cells and or for and or and was by a of a of the cognate and or a and These results are of The of pIγRE of the to the sites us to investigate the importance of the ICAM-1 pIγRE palindromic in the regulation of theICAM-1 gene by the potent tyrosine phosphatase the ICAM-1 reporter a 5′ deletion mutant of that of the ICAM-1 promoter or a carrying a site-specific in pIγRE It is that the first of the ICAM-1 is as as the ICAM-1 promoter to the expression of a reporter gene in response to and in the induction was the site-specific mutant as the 5′ deletion mutant and by of cells the specific of transcription factors to the ICAM-1 pIγRE from that and leads to a complex of The complex was by the of a of an pIγRE by a leads to of STAT-1 that to the pIγRE element in the ICAM-1 pIγRE was from cells and or for and or was by a of a of the cognate pIγRE and or a also specific for STAT-1 or and These results are of It has been demonstrated that of both STAT-1 and factors to the pIγRE element in the ICAM-1 promoter J.L. Quinlan K.L. Paxton L.L. Naik S.M. Caughman J. Invest. 1997; Full Text PDF PubMed Scopus Google E. J. van de Stolpe A. W. van der Saag P.T. J. Biol. Full Text PDF PubMed Google Scholar). we the complex is of STAT-3, or both by from and cells and or and the ICAM-1 STAT-1 the and a of the complex and the complex by and These results suggest that results in the of a complex of ICAM-1 pIγRE and STAT-1 transcription ICAM-1 gene expression is regulated by numerous and or factors and The of the ICAM-1 promoter is complex and is regulated by an between different transcription factors such as NF-κB, Ets, C/EBP, and as demonstrated in various cell myeloid cells, B lymphocytes, cells, and cells (7van de Stolpe A. van der Saag P.T. J. Mol. Med. 1996; 74: 13-33Crossref PubMed Scopus (648) Google Scholar, 8Roebuck K.A. Finnegan A. J. Leukocyte Biol. 1999; 66: 876-888Crossref PubMed Scopus (462) Google Scholar). that protein be involved gene expression. In human and human cell acid and phosphatases ICAM-1 and J. Res. 1996; PubMed Scopus Google Scholar). In addition, and been shown to the cell surface adhesion molecules and S. S. J. Immunol. 1997; PubMed Scopus Google Scholar). that the induction of ICAM-1 gene expression J.L. Quinlan K.L. Paxton L.L. Naik S.M. Caughman J. Invest. 1997; Full Text PDF PubMed Scopus Google Scholar). to many different pathways in T cells, tyrosine been in the regulation of ICAM-1 gene expression. In we the role of tyrosine in regulation of the ICAM-1 promoter in human T cells. The as of the potent PTP inhibitors, was in to the equilibrium between PTP and protein-tyrosine kinases and to increase results first demonstrated that was in ICAM-1 surface expression. that compound was to increase both the of cells and the The of the was by the that leads to the induction of ICAM-1 expression in T cell and also in primary human experiments that the of on ICAM-1 activity are of PTP such results are a that molecules are more potent of human immunodeficiency promoter activity B. R. N. G. M. R. M. J. Biol. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). These observations suggest that the of on PTP be from of in of are to on from several that the transcription is a role in the induction of ICAM-1 N. B. C. J. Audette M. Cell 1997; Google Scholar, S. C. U. N. Caughman K. J. Invest. 1995; Full Text PDF PubMed Scopus Google Scholar, D. J. 1995; PubMed Scopus Google Scholar, S. van de Stolpe A. E. van der Saag Immunobiology. 1997; PubMed Scopus Google that is following and J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, de Stolpe A. E. Johnson van der Saag P.T. J. Biol. Full Text PDF PubMed Google Scholar, N.D. Mol. Cell. Biol. PubMed Google Scholar). This family of factors has the to other factors such as C/EBP, and N.D. A.B. J. PubMed Scopus Google Scholar, B. Mol. Cell. Biol. PubMed Google Scholar, B. J. PubMed Scopus Google Scholar). results are in these observations we that is a in bpV[pic]-mediated expression of ICAM-1 in human T cells. and A. C. D. B. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google that the PTP can tyrosine of of experiments a form of us to that and activation of is on both and of This of is to be to of from through of and by the also that bpV[pic]-mediated activation of ICAM-1 gene expression is on both and family These are that the ICAM-1 and J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google S. van de Stolpe A. E. van der Saag Immunobiology. 1997; PubMed Scopus Google Scholar). we of the between the level and induction of ICAM-1 expression in T cells, the various between and other transcription factors to the ICAM-1 promoter and to be The been to be involved in activation of the ICAM-1 promoter in various cell human and cell K.A. A. K. A.B. J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Audette M. H. S. 1998; PubMed Scopus Google Scholar). the of factors in activation of we cells or results demonstrated that following a in the or sites a carrying the sites both sites the up-regulation of ICAM-1 luciferase activity was results are that a in the strongly the activity Audette M. H. S. 1998; PubMed Scopus Google Scholar). In was demonstrated that expression for and ICAM-1 transcription in cells, and the activation of ICAM-1 transcription was strongly using a In addition, a of the the induction of ICAM-1 gene expression. are at that such a experiments by de and Audette M. H. S. 1998; PubMed Scopus Google using cell different from the in the in to that is on of and we of The that both sites in the are important for bpV[pic]-mediated induction of ICAM-1 transcription an of activation is of a interaction between sites for and transcription This is by a that the element in the ICAM-1 promoter is of the and sites K.A. A. K. A.B. J. Biol. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). a activation of ICAM-1 by retinoic acid and is to a between retinoic acid response elements and sites Cell Res. 1998; PubMed Scopus Google Scholar). are to the in theICAM-1 promoter that sites to form the In to sites for and transcription factors, results that the signaling is also in the induction of ICAM-1 expression in human T cells that is the potent PTP a in the element bpV[pic]-mediated up-regulation of ICAM-1 promoter also demonstrated that was in of results are a that the PTP the protein-tyrosine kinases in tyrosine of STAT-3, and S.J. W. K. J.M. Sci. U. S. A. 1997; PubMed Scopus Google Scholar). for the STAT-1 has been shown to be by a PTP Sci. U. S. A. 1999; PubMed Scopus Google Scholar). can be that the PTP in of STAT-1 in the to the and the for a of a level of STAT-1 in an In that ICAM-1 gene expression in human T cells is the of constitutive PTP to ICAM-1 expression at a more of the transcription factors involved in bpV[pic]-mediated activation of ICAM-1 expression be to the various the activation of the ICAM-1 gene in human T cells. for of the M. for in and de for the reporter of the ICAM-1 promoter and W. C. for R. Rothlein for and N. for

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