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

Abstract

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 factorlike 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 contained cis-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-␥ inducibility. Some of the potential regulatory motifs and other unknown cis elements may be involved in the constitutive expression, and LPS and interferon-␥ inducibilities. The mCD156 gene was mapped to chromosome 7, region F3-F4.The mouse CD156 (mCD156) 1 (MS2) and human CD156 are type I transmembrane glycoproteins found on myelomonocytic cell lineage (1, 2). 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 en-

Comparative microarray analysis of gene expression during apoptosis-induction by growth factor deprivation or protein kinase C inhibition

“…Evidence for overlapping proteolytic activities in the two apoptotic model pathways came from our ®nding that CD156, a member of the ADAM family of metallo-protease/disintegrin domain containing proteins (Kataoka et al, 1997) was induced in both pathways. Additionally, one of the most signi®cantly repressed genes we found was SPI2/EB1, coding for a serine proteinase inhibitor related to contrapsin (Inglis et al, 1991).…”

CD156 Transgenic Mice

“…The infiltration of leukocytes is a multi-step process involving (1) the sticking of leukocytes to venular endothelial cells, (2) penetration of the endothelial cell junction and basement membrane, and (3) chemotactic migration toward the inflammatory stimulus. Although the roles of cell adhesion molecules and chemotactic factors are now becoming apparent [8,9], the molecular basis of the leukocyte emigration, in particular the second step, is not well understood, because of the limitation of methodologies to elucidate this step.…”

“…CD156 is a type I transmembrane glycoprotein found in myelomonocytic cell lineages [1][2][3][4] and a member of a family of proteins (ADAM), which are characterized by the conserved structure of type 3 hemorrhagic snake venom proteins consisting of a metalloprotease domain containing zinc-binding consensus histidine and protease catalytic glutamic residues, a disintegrin domain containing a platelet aggregation inhibitor-like structure, and a cysteine-rich region. In addition, the extracellular region of CD156 is followed by a transmembrane region and a proline-rich cytoplasmic tail containing a consensus SH3 (Src homology 3)-binding sequence.…”

ADAMTS-1 Protein Anchors at the Extracellular Matrix through the Thrombospondin Type I Motifs and Its Spacing Region

“…In contrast, the ADAMTS-1 protein does not contain a transmembrane domain but possesses three thrombospondin (TSP) type I motifs, which are the conserved motifs in both thrombospondin 1 and 2 (19), at its carboxylterminal region. The analyses of the genomic structure of AD-AMTS-1 showed that it is markedly different from those of MDC and MS2 (20,21), suggesting that ADAMTS-1 may be a distant member of the ADAM family. Because in vivo administration of lipopolysaccharide significantly enhanced the expression of ADAMTS-1 mRNA in kidney and heart, it is presumed that ADAMTS-1 might be involved in the inflammatory reaction (17).…”