Structure of the Murine CD156 Gene, Characterization of Its Promoter, and Chromosomal Location

The murine cell surface antigen mCD156 is a glycoprotein that is expressed in monocytic cell lines and consists of a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, and an epidermal growth factor-like domain in the extracellular region. The mCD156 gene is composed of 24 exons and 23 introns and spans approximately 14 kilobases. The first exon encodes most of the signal peptide sequence, and the transmembrane region is encoded by a single exon (19). In contrast, the other regions are composed of multiple exons. Of these, exons 7–12 and 12–15 encode a metalloprotease domain and a disintegrin domain, respectively. Sequence analysis of the 5′-flanking DNA revealed many potential regulatory motifs. Chloramphenicol acetyltransferase analysis demonstrated that nucleotides at positions −183, −334, and −623 containedcis-acting enhancing elements in a mouse monocytic cell line, aHINS-B3. Nucleotides at positions −183 and −390 contained elements responsible for lipopolysaccharide (LPS) inducibility, although several other 5′-flanking regions were also involved in LPS responsiveness. Regions −202, −507, and −659 play a role in interferon-γ inducibility. Some of the potential regulatory motifs and other unknown cis elements may be involved in the constitutive expression, and LPS and interferon-γ inducibilities. The mCD156 gene was mapped to chromosome 7, region F3-F4. The murine cell surface antigen mCD156 is a glycoprotein that is expressed in monocytic cell lines and consists of a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, and an epidermal growth factor-like domain in the extracellular region. The mCD156 gene is composed of 24 exons and 23 introns and spans approximately 14 kilobases. The first exon encodes most of the signal peptide sequence, and the transmembrane region is encoded by a single exon (19). In contrast, the other regions are composed of multiple exons. Of these, exons 7–12 and 12–15 encode a metalloprotease domain and a disintegrin domain, respectively. Sequence analysis of the 5′-flanking DNA revealed many potential regulatory motifs. Chloramphenicol acetyltransferase analysis demonstrated that nucleotides at positions −183, −334, and −623 containedcis-acting enhancing elements in a mouse monocytic cell line, aHINS-B3. Nucleotides at positions −183 and −390 contained elements responsible for lipopolysaccharide (LPS) inducibility, although several other 5′-flanking regions were also involved in LPS responsiveness. Regions −202, −507, and −659 play a role in interferon-γ inducibility. Some of the potential regulatory motifs and other unknown cis elements may be involved in the constitutive expression, and LPS and interferon-γ inducibilities. The mCD156 gene was mapped to chromosome 7, region F3-F4. The mouse CD156 (mCD156) 1The abbreviations used are: mCD156, murine CD156; kb, kilobase(s); MTP, metalloprotease; LPS, lipopolysaccharide; IFN, interferon; bp, base pair(s); Pipes, 1,4-piperazinediethanesulfonic acid; CAT, chloramphenicol acetyltransferase; CR, cysteine-rich; EGF, epidermal growth factor; NF, nuclear factor; IL, interleukin; FISH, fluorescent in situ hybridization; DAPI, 4′,6-diamidino-2-phenylindole. (MS2) and human CD156 are type I transmembrane glycoproteins found on myelomonocytic cell lineage (1Yoshida S. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. Int. Immunol. 1990; 2: 585-591Crossref PubMed Scopus (107) Google Scholar, 2Yoshiyama K. Higuchi H. Kataoka M. Matsuura K. Yamamoto S. Genomics. 1997; 41: 56-62Crossref PubMed Scopus (92) Google Scholar). The mCD156 cDNA is 3.2 kb long with an open reading frame encoding 826 amino acids. The extracellular region consisting of 644 amino acids has a metalloprotease (MTP) domain containing the zinc-binding consensus histidine and protease catalytic glutamic residues and a disintegrin domain containing a platelet aggregation inhibitor-like structure, whereas the cytoplasmic region consisting of 143 amino acids contains a proline-rich amino acid sequence containing consensus SH3 (Src homology 3) binding sequence. mCD156 plays a role in infiltration of leukocytes by leukocyte adhesion to endothelial cells and degradation of vascular basement membrane (3Higuchi Y. Kataoka M. Yamamoto S. Tissue Antigens. 1997; 48 (423): 423Google Scholar). CD156 is a member of a family of proteins (ADAM) which are characterized by a conserved structure in hemorrhagic snake venom proteins. Following our report of mCD156 (ADAM 8), a number of ADAMs have been reported (1Yoshida S. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. Int. Immunol. 1990; 2: 585-591Crossref PubMed Scopus (107) Google Scholar, 4Blobel C.P. Wolfsberg T.G. Turck C.W. Myles D.G. Primakoff P. White J.M. Nature. 1992; 356: 248-252Crossref PubMed Scopus (612) Google Scholar, 5Heinlein U.A.O. Wallat S. Senftleben A. Lamaire L. Dev. Growth & Differ. 1994; 36: 49-58Crossref Scopus (53) Google Scholar, 6Wolfsberg T.G. Straight P.D. Gerena R.L. Huovila A.-P. Primakoff P. Myels D.G. White J.M. Dev. Biol. 1995; 169: 378-383Crossref PubMed Scopus (360) Google Scholar, 7Perry A.C.F. Jones R. Barker P.J. Hall L. Biochem. J. 1992; 286: 671-675Crossref PubMed Scopus (81) Google Scholar, 8Wolfsberg T.G. Primakoff P. Myles D.G. White J.M. J. Cell Biol. 1995; 131: 275-278Crossref PubMed Scopus (443) Google Scholar, 9Nomura N. Miyajima N. Sazuka T. Tanaka A. Kawarabayashi Y. Sato S. Nagase T. Seki N. Ishikawa K. Tabata S. DNA Res. 1994; 1: 27-35Crossref PubMed Scopus (272) Google Scholar, 10Weskamp G. Kratzschmar J. Reid M.S. Blobel C.P. J. Cell Biol. 1996; 132: 717-726Crossref PubMed Scopus (185) Google Scholar, 11Howard L. Lu X. Griffiths S. Glynn P. Biochem. J. 1996; 317: 45-50Crossref PubMed Scopus (105) Google Scholar, 12Emi M. Katagiri T. Harada Y. Saito H. Inazawa I. Ito F. Kasumi F. Nakamura Y. Nat. Genet. 1993; 5: 151-157Crossref PubMed Scopus (98) Google Scholar, 13Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (439) Google Scholar, 14Kratzschmar J. Lum L. Blobel C.P. J. Biol. Chem. 1996; 271: 4593-4596Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar). ADAMs 1–7 are expressed in reproductive organs, mainly the testes, and are implicated in sperm-egg fusion and spermatogenesis. ADAMs 8–12 (meltrin-α) and 15 (metargidin) are of non-reproductive cell origin, including myeloid, muscle, brain, and breast cells. ADAM 12 has been shown to mediate myocyte cell fusion. Recently, a new family member designated TACE has been reported to function as a tumor necrosis factor-α-converting enzyme that liberates 17-kDa tumor necrosis factor-α from 26-kDa membrane-bound pro-tumor necrosis factor-α (15Black R.A. Rauch C.T. Kozlosky C.J. Peschon J.J. Slack J.L. Wolfson M.F. Castner B.J. Stocking K.L. Reddy P. Srinivasan S. Nelson N. Boiani N. Schooley K.A. Gerhart M. Davis R. Fitzner J.N. Johnson R.S. Paxton R.J. March C.J. Cerretti D.P. Nature. 1997; 385: 729-733Crossref PubMed Scopus (2728) Google Scholar, 16Moss M.L. Jin C. Milla M.E. Bickett D.M. Burkhart W. Carter H.L. Chen W.-J. Clay W.C. Didsbury J.R. Hassler D. Hoffman C.R. Kost T.A. Lambert M.H. Leesnitzer M.A. McCauley P. McGeehan G. Mitchell J. Moyer M. Pahel G. Rocque W. Overton T. Su T.-L. Warner J. Willard D. Becherer J.D. Nature. 1997; 385: 733-736Crossref PubMed Scopus (1490) Google Scholar). TACE activity is also found in ADAM 10, which is originally separated as an enzyme for degradation of myelin basic protein (17Lunn C.A. Fan X. Dalie B. Miller K. Zavodny P.J. Narula S.K. Lundell D. FEBS Lett. 1997; 400: 333-335Crossref PubMed Scopus (122) Google Scholar). Another new family protein designated ADAMST-1 appears to contain thrombospondin-like structures and play a role in tumor cell migration (18Kuno K. Kanada N. Nakashima E. Fujiki F. Ichimura F. Matsushima K. J. Biol. Chem. 1997; 272: 556-562Abstract Full Text Full Text PDF PubMed Scopus (442) Google Scholar). We report here the isolation and characterization of the mCD156 gene and the presence of the cell type-specific, lipopolysaccharide (LPS) and interferon (IFN)-γ-inducible promoter activities in its 5′ upstream sequence. We have also determined the mCD156 gene location. Restriction enzymes were purchased from Takara (Kyoto, Japan), Toyobo (Osaka, Japan), Life Technologies, Inc. (Gaithersburg, MD), and Wako Pure Chemicals (Osaka, Japan). Agarose ultrapure DNA grade was from Takara. The DNA ligation kit, reverse transcriptase, S1 nuclease, and mung bean nuclease were obtained from Takara, and bovine alkaline phosphatase was obtained from Boehringer Mannheim (Tokyo, Japan). LPS (Escherichia coli serotype 055:B5) was obtained from Sigma Chemical Co. (St. Louis, MO). Mouse IFN-γ was purchased from Genzyme (Cambridge, MA). Radioactive nucleotides [α-32P]dCTP (3,000 Ci/mmol) and [γ-32P]ATP (6,000 Ci/mmol) were obtained from NEN Life Science Products. Chemicals used for DNA sequencing were obtained from Toyobo. X-ray film (XAR-351) was obtained from Kodak (Rochester, NY). Murine macrophage cell line aHINS-B3 and murine glioblastoma cell line G203 were grown in Dulbecco's modified Eagle's medium containing fetal calf serum. The bacteriophage murine was as K. T. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar, Y. Setoguchi M. S. Higuchi Y. Akizuki S. Yamamoto S. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar). DNA from murine was by The DNA in the of kb were the of The DNA was a and the was grown in E. coli and as Radioactive were by cDNA from an mCD156 (1Yoshida S. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. Int. Immunol. 1990; 2: 585-591Crossref PubMed Scopus (107) Google M. C. P. J. Biol. PubMed Scopus Google with a activity of of containing were to the of and Davis Davis PubMed Scopus Google at in for and with at for The were to Kodak film with a at for were by DNA and were obtained as by T. J. Scholar). DNA from the DNA of were The were and for 12 at a ligation purchased from Takara. The DNA was used to cells. White were were determined by F. S. S. A. PubMed Scopus Google Scholar, M. Higuchi Y. S. N. S. Akizuki S. Yamamoto S. Biol. PubMed Scopus Google DNA with as in the were determined on DNA in used as for sequencing were an DNA were determined on S1 nuclease was to a modified of and Full Text PDF Scopus Google Scholar). DNA to containing the region from the 5′ upstream to of the mCD156 gene was as a and with an a to to of the first exon of the mCD156 The DNA was with and of the coli DNA for at The was to for to the and on with and the was separated on alkaline from aHINS-B3 was for at with the in Pipes, and Following the was with S1 nuclease and and of S1 nuclease was The was for at The was by the of and and the were with with in to and on a The for analysis was the single used in the S1 nuclease was from aHINS-B3 cells. The was to of by the for 15 at in of containing and The was and in reverse in the presence of of reverse transcriptase, and of at the were in to and on a sequencing containing the nucleotides to to of the 5′ exon and sequence of the mCD156 gene was with and The in the DNA was with were and with of mung bean nuclease for at the were with mung bean nuclease for at The were with the by DNA the of was as K. T. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). was with and of the containing containing the nucleotides to to was with and to with mung bean nuclease, and as DNA was with DNA DNA was by alkaline by to DNA was the mouse macrophage line aHINS-B3 and the mouse glioblastoma line G203 by as K. T. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). were at a of the gene and the containing the gene was in and to the the cells were a by a with medium was and the for 24 24 the cells were with LPS IFN-γ for and 24 respectively. were with with for on by and and in of were by and were and for protein to the of Biochem. PubMed Scopus Google Scholar). was as K. T. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). The was with and of for at and the were separated by The activity for was to activity from the The activity for was expressed as a of that of type with Mouse were to a R. A. T. 1994; Google Scholar). were from mouse and at in medium with fetal calf LPS, and the were with for an 14 The cells were and at for in medium with were by the used for human chromosome and The DNA of containing a the regions the most 5′ were with the Life Technologies, Inc. 1993; PubMed Scopus Google Scholar). The for was to the of J. S. A. 1992; PubMed Scopus Google and and 1993; PubMed Scopus Google Scholar). were at for the were in in for at by with The was at for in a consisting of and human I and at for 15 The was on the were and as as a and the were by and the of the with was by on J. S. A. 1992; PubMed Scopus Google Scholar, on Google Scholar). The mCD156 was kb from which mCD156 cDNA was and characterized (1Yoshida S. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. Int. Immunol. 1990; 2: 585-591Crossref PubMed Scopus (107) Google Scholar). from of mouse DNA was mCD156 designated and were for and sequence analysis of that contained the 5′ of the for mCD156 for the of the whereas contained a the regions the most 5′ The mCD156 gene is composed of 14 kb, 24 exons and 23 is a line of the of the The introns in from to introns and on the 5′ and of the and a of exons is found of revealed that the consensus sequence R. P. Biochem. PubMed Scopus Google at the was by approximately of the of the gene for amino of the mCD156 I are the sequence. in a new are the sequence. are with of a protein R. P. Biochem. PubMed Scopus Google as in the J. P. Carter C. K. M. L. R. Full Text PDF PubMed Scopus Google Scholar). the exon of the mCD156 gene is on the protein structure and The mCD156 protein is composed of a signal a an MTP, a a CR, an EGF, a and a cytoplasmic The first exon encodes most of the signal peptide sequence, and the transmembrane domain is encoded by a single exon M. Higuchi Y. S. N. S. Akizuki S. Yamamoto S. Biol. PubMed Scopus Google Scholar). In contrast, other regions are of multiple exons. encode a exons an exons a disintegrin exons a domain, including an domain exons The cytoplasmic region a proline-rich amino acid that is encoded by exons The residues that have and the region are encoded by exon The of the ADAM gene has been reported T. Harada Y. M. Nakamura Y. Cell Genet. 1995; PubMed Scopus Google Scholar). The of its exons and introns were and of the mCD156 amino acids encoded by exon mCD156 and ADAM is of that 12 exons of 24 of mCD156 to the regions of exons of ADAM for the exons and of the mCD156 gene to that exons and of the ADAM The of the mCD156 gene were by S1 nuclease DNA to the region from to an was The the presence of a approximately nucleotides upstream of the The demonstrated by S1 nuclease was by was used for from aHINS-B3 cells and reverse single nucleotides upstream of the was which the S1 nuclease The 5′ upstream region contained a number of potential regulatory as shown in elements were at positions to from the from the sequence by a in the and although and are in and are with in the human promoter contains a K. T. PubMed Scopus Google Scholar). and are found although appears to be to from the Another regulatory the is at positions to and to binding for are the in as are upstream S.K. G. M.S. J.L. K.L. Full Text PDF Scopus Google Scholar). The and its reverse are found at positions to to to and to Full Text PDF PubMed Scopus Google Scholar). The that is by the macrophage and which is to the A. S. R.A. 1990; Full Text PDF PubMed Scopus Google is at positions to and to binding at positions to Res. PubMed Scopus Google Scholar). The is found at positions to and to The is in many as mouse and protein D. R. M. Res. PubMed Scopus Google and in the The binding and its reverse sequence are at positions to to and to of and its reverse sequence in the region and Y. M.F. K. Biol. 1993; PubMed Scopus Google Scholar). interferon regulatory binding sequence is at positions to T. S. H. T. 41: Full Text PDF PubMed Scopus Google Scholar, J. P. H. C. 41: Full Text PDF PubMed Scopus Google Scholar, B. D. D. P. J. J. PubMed Scopus Google Scholar). elements with at positions to K. B. Biol. PubMed Scopus Google Scholar, J. Biol. PubMed Scopus Google Scholar). The upstream sequence to has consensus regulatory the regions for of the of the 5′-flanking region to the gene as a gene and The were aHINS-B3 which and G203 which The region including upstream of the was of in aHINS-B3 whereas containing upstream of the a of the upstream sequence the gene the gene by including to of the 5′ upstream sequence the gene expression, the a was in G203 cells. We that of in mouse macrophage cell line is by LPS and mouse IFN-γ (1Yoshida S. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. Int. Immunol. 1990; 2: 585-591Crossref PubMed Scopus (107) Google Scholar). We the of LPS and IFN-γ on The aHINS-B3 and G203 cells were with LPS for in aHINS-B3 cells with and with LPS was and were also of the of and was of The aHINS-B3 cells were with IFN-γ for 24 activities in aHINS-B3 cells with and were with in G203 cells was by LPS and IFN-γ the the was for the on of the the was used to the the the signal from the and the mouse chromosome was The was determined on the from to the gene is at chromosome 7, region F3-F4. of the is in B. The mouse chromosome in human including 10, and The human and mouse have been mapped to human chromosome and mouse chromosome 7, and the human and mouse have been mapped to human chromosome and mouse chromosome 7, Nat. Genet. 1993; PubMed Scopus Google Scholar). with human CD156 is a human K. Higuchi H. Kataoka M. Matsuura K. Yamamoto S. Genomics. 1997; 41: 56-62Crossref PubMed Scopus (92) Google and mouse We have characterized the structure and determined the of the mCD156 The gene spans approximately 14 kb and consists of 24 exons and 23 The exon of gene encode the mCD156 (MS2) cDNA that been from mouse myelomonocytic cells (1Yoshida S. Setoguchi M. Higuchi Y. Akizuki S. Yamamoto S. Int. Immunol. 1990; 2: 585-591Crossref PubMed Scopus (107) Google Scholar). The of as determined by S1 nuclease and with the of a at to the 5′-flanking sequence of the mCD156 that with that were also the 5′-flanking region of the analysis the of several regions that the of the mCD156 gene in aHINS-B3 cells in the presence of LPS We also the mCD156 gene to mouse chromosome 7, region F3-F4. We the human CD156 gene to the region of chromosome K. Higuchi H. Kataoka M. Matsuura K. Yamamoto S. Genomics. 1997; 41: 56-62Crossref PubMed Scopus (92) Google an to mouse chromosome 7, region the region of chromosome on which the mCD156 gene is ADAM has been mapped to human chromosome many including the and region are mapped Nat. Genet. 1993; PubMed Scopus Google Scholar, Miller A. 1993; PubMed Scopus Google Scholar). the mouse of in chromosome which also of human 7, and of by and are for ADAM for encode amino which a transmembrane and cytoplasmic whereas that for encodes a protein of amino acids which contain regions from to the cytoplasmic region T. Harada Y. M. Nakamura Y. Cell Genet. 1995; PubMed Scopus Google Scholar). The and number of exons in the gene are to of the mCD156 although exon of has of exons and 24 for a domain is encoded by multiple exons including and an domain by exons a disintegrin domain by exons a domain including an by exons a transmembrane domain by exon and a cytoplasmic domain by exons 24 and of amino acids mCD156 and ADAM revealed that 12 exons of in in region of mCD156 to of ADAM the ADAM family are from the the mouse ADAMs and have been mapped to and C. Primakoff P. White J.M. Myles D.G. Genomics. 1996; PubMed Scopus Google ADAM to be to ADAM family proteins are a of proteins a hemorrhagic snake structure, with a cell including muscle, brain, and and a T.G. Primakoff P. Myles D.G. White J.M. J. Cell Biol. 1995; 131: 275-278Crossref PubMed Scopus (443) Google Scholar, A.-P. White J.M. Cell Biol. 1996; PubMed Scopus Google Scholar). and cytoplasmic have been on the of ADAMs with the of and new have been be to ADAMs on the of structure and The family of ADAMs (ADAM 10, and plays a role in the protein degradation by of activity L. Lu X. Griffiths S. Glynn P. Biochem. J. 1996; 317: 45-50Crossref PubMed Scopus (105) Google Scholar, R.A. Rauch C.T. Kozlosky C.J. Peschon J.J. Slack J.L. Wolfson M.F. Castner B.J. Stocking K.L. Reddy P. Srinivasan S. Nelson N. Boiani N. Schooley K.A. Gerhart M. Davis R. Fitzner J.N. Johnson R.S. Paxton R.J. March C.J. Cerretti D.P. Nature. 1997; 385: 729-733Crossref PubMed Scopus (2728) Google Scholar, 16Moss M.L. Jin C. Milla M.E. Bickett D.M. Burkhart W. Carter H.L. Chen W.-J. Clay W.C. Didsbury J.R. Hassler D. Hoffman C.R. Kost T.A. Lambert M.H. Leesnitzer M.A. McCauley P. McGeehan G. Mitchell J. Moyer M. Pahel G. Rocque W. Overton T. Su T.-L. Warner J. Willard D. Becherer J.D. Nature. 1997; 385: 733-736Crossref PubMed Scopus (1490) Google Scholar, J. D. T. 1996; PubMed Scopus Google Scholar). The family and has a region to fusion peptide and is involved in membrane fusion C.P. Wolfsberg T.G. Turck C.W. Myles D.G. Primakoff P. White J.M. Nature. 1992; 356: 248-252Crossref PubMed Scopus (612) Google Scholar, 13Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (439) Google Scholar). The family (ADAM cell The family 10, and proteins containing SH3 G. Kratzschmar J. Reid M.S. Blobel C.P. J. Cell Biol. 1996; 132: 717-726Crossref PubMed Scopus (185) Google Scholar, 11Howard L. Lu X. Griffiths S. Glynn P. Biochem. J. 1996; 317: 45-50Crossref PubMed Scopus (105) Google Scholar, 13Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (439) Google Scholar, 14Kratzschmar J. Lum L. Blobel C.P. J. Biol. Chem. 1996; 271: 4593-4596Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar). mCD156 also to the cytoplasmic of mCD156 has proline-rich to SH3 motifs. The ADAMs and and of cells including and cells A.C.F. Jones R. Barker P.J. Hall L. Biochem. J. 1992; 286: 671-675Crossref PubMed Scopus (81) Google Scholar, 13Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (439) Google Scholar, J. D. T. 1996; PubMed Scopus Google Scholar). ADAM family proteins be in the Some regions −183, −334, and −623 contained the to contains a the to has been shown to play a role in of H.L. R.J. Chen R.A. D.G. J. Biol. Chem. 1993; Full Text PDF PubMed Google macrophage C.J. Chen D.G. Biol. 1994; PubMed Scopus Google Y. Biol. 1995; PubMed Google R. R. M. J. 1994; PubMed Scopus (81) Google and R. D.P. C. J. 1994; PubMed Scopus Google Scholar). that the regions −183, −334, and −623 are involved in the cell of the mCD156 The sequence, and binding are in the region −623 to −507, whereas and are found in the region −183 to The regions −183 and −390 the to LPS, although many other regions also to contain elements responsible for LPS inducibility. elements including M.A. P. J. 1990; PubMed Scopus Google Scholar, Y. T.A. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, C.J. P. S. A. 1993; PubMed Scopus Google H. Biol. PubMed Scopus Google M.L. S. Biol. 1994; PubMed Scopus Google and C.J. P. S. A. 1993; PubMed Scopus Google binding have been shown to mediate to LPS in several although the role of and binding is C. T. S. A. 1990; PubMed Scopus Google Scholar, T. S. K. M. Y. N. H. S. N. T. 1995; Scholar). Of these, the 5′-flanking region contains binding binding may be involved in LPS inducibility, although the regions −183 and −390 have other elements may LPS responsiveness. regions play a role in in the regions and −659 The 5′ upstream region of the mCD156 gene contains elements responsible for IFN-γ as binding Y. T.A. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, T. S. K. M. Y. N. H. S. N. T. 1995; and J. J. PubMed Scopus Google Scholar). of elements is found in the analysis is to regions for responsiveness. We M. Setoguchi for and T. for the