LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors

Stacey, Martin; Lin, Hsi‐Hsien; Gordon, Siamon; McKnight, Andrew J.

doi:10.1016/s0968-0004(00)01583-8

Cited by 171 publications

(155 citation statements)

References 45 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…4 -7 CD97 consists of an extended extracellular region with several N-terminal epidermal growth factor (EGF) domains coupled to the TM7 domain by a stalk. 1,8 Various CD97 isoforms exist possessing 3 (EGF 1,2,5), 4 (EGF 1,2,3,5), or 5 (EGF 1,2,3,4,5) EGF domains. CD97 binds to membrane receptor CD55.…”

mentioning

confidence: 99%

N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding

Wobus

Vogel

Schmücking

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

CD97 is an EGF-TM7 receptor found on various carcinomas where expression levels correlate with dedifferentiation and tumor stage, smooth muscle cells and leukocytes. CD97 acts as an adhesion molecule by binding to its cellular ligand, CD55. In this study, we demonstrate that 2 immunodominant CD97 epitopes are not equally present in the various cell types. Differences were apparent in gastrointestinal tumors and smooth muscle cells where monoclonal antibodies (mAbs) to the first epidermal growth factor (EGF) domain (CD97 EGF ) showed a more restricted staining pattern than mAbs to the stalk region (CD97 stalk ). This discrepancy was not detectable in cultured gastrointestinal tumor cell lines. In fact, the selection of the CD97 mAb influences the result of clinical studies. Thus, we clarified the reason(s) for these differences in CD97 mAb staining on various cell types. We provide evidence that epitope accessibility for CD97 EGF Key words: CD97; colorectal cancer; smooth muscle cell; epitope accessibility; glycosylation CD97 is a member of a subfamily of 7-span transmembrane (TM7) receptors referred to as EGF-TM7 proteins. 1,2 In normal tissues, CD97 is abundantly expressed in smooth muscle cells, macrophages, granulocytes, dendritic cells and in some T and B cells. 3 Carcinomas of different origin showed higher CD97 expression compared to the corresponding normal cell types. 4 -7 CD97 consists of an extended extracellular region with several N-terminal epidermal growth factor (EGF) domains coupled to the TM7 domain by a stalk. 1,8 Various CD97 isoforms exist possessing 3 (EGF 1,2,5), 4 (EGF 1,2,3,5), or 5 (EGF 1,2,3,4,5) EGF domains. CD97 binds to membrane receptor CD55. 9 This interaction is mediated by the first 2 CD97 EGF domains. 9 -11 Chondroitin sulfate glycosaminoglycan, present in cell membranes and the extracellular matrix, is a new ligand to the longest CD97 isoform (EGF 1,2,3,4,5). 12 The ability of CD97 EGF domains to interact with cellular and/or extracellular matrix ligands suggests that the molecule is involved in cell-cell or cell-matrix interactions. Various lines of evidence have shown an important role for CD97 in tumor dedifferentiation, migration, invasiveness and metastasis. CD97 levels correlate with the in vitro migration and invasion capacity of colorectal tumor cell lines and CD97-transfected cells. 6 Colorectal carcinomas with more strongly CD97-stained, scattered tumor cells at the invasion front showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. 6 In thyroid cancers, CD97 expression parallels the aggressiveness and lymph node involvement of these tumors. 4,5 Our previous data revealed that CD97 has prognostic and therapeutic potential in cancer. However, analyzing CD97 expression brings up the phenomenon that different staining patterns, depending on which CD97 monoclonal antibody (mAb) has been used for immunohistology, can be readily observed in pancreatic tissues. 7,13 Based on this observation, one aim of ...

show abstract

mentioning

confidence: 99%

N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding

Wobus

Vogel

Schmücking

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The predicted overall structure of EMR4 ( Fig. 2A) is similar to other members of the EGF-TM7 family [1,2]. Pairwise comparison revealed an amino acid sequence identity of 45% with EMR3 [11], 38% with EMR2 [10], 34% with EMR1 [7], 29% with CD97 [3,4] and 26% with ETL [13].…”

Section: Cdna Cloning Sequence Analysis and Chromosomal Localizationmentioning

confidence: 69%

“…The EGF-TM7 family is a group of class B seven-span transmembrane (TM7) receptors predominantly expressed by cells of the immune system [1,2]. Family members CD97, EGF module-containing mucin-like receptor (EMR) 1-4 and EGF-TM7-latrophilin-related protein (ETL) are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains [3][4][5][6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inactivation of the EGF‐TM7 receptor EMR4 after the Pan‐Homo divergence

Hamann¹,

Kwakkenbos²,

Jong³

et al. 2003

Eur J Immunol

View full text Add to dashboard Cite

We here report on the identification of a novel human EGF-TM7 receptor, designated EMR4. Like most EGF-TM7 receptor genes, EMR4 is localized on the short arm of chromosome 19, in close proximity to EMR1. Remarkably, due to a one-nucleotide deletion in exon 8, translation of human EMR4 would result in a truncated 232-amino acid protein lacking the entire seven-span transmembrane region. This deletion is not present in nonhuman primates, including chimpanzees, suggesting that EMR4 became nonfunctional only after human speciation, about five million years ago. Thus, EMR4 surprisingly accounts for a genetic difference between humans and primates related to immunity.

show abstract

“…CD97 belongs to a family of G-protein coupled receptors (GPCRs) with an unusual large Nterminal extracellular domain (LNB-TM7) (Kwakkenbos et al, 2004;Stacey et al, 2000) and is the founding member of a small subfamily, the EGF-seven-transmembrane (EGF-TM7) receptors (Eichler et al, 1994;Hamann et al, 1995). It consists of a variable number of Nterminally located EGF-domains, a long extracellular stalk, the TM7 and a short intracellular region.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle cells

Wobus

Wandel

Prohaska

et al. 2008

Gene

View full text Add to dashboard Cite

The EGF-TM7 receptor CD97 shows different features of expression and function in muscle cells compared to hematopoetic and tumor cells. Since the molecular function and regulation of CD97 is poorly understood, this study aimed at defining its basal transcriptional regulation in smooth muscle cells (SMCs).The computational analysis of the CD97 5'-flanking region revealed that the TATA boxlacking promoter possesses several GC-rich regions as putative Sp1/Sp3 binding sites.Transfection studies with serially deleted promoter constructs demonstrated that the minimal promoter fragment resided in the -218/+45 region containing one out of five identified GCboxes in the leiomyosarcoma cell line SK-LMS-1 and human bronchial smooth muscle cells (HbSMCs). Mutation of the most proximal GC-site in CD97 reporter gene constructs caused a significant decrease in promoter activity. Gel shift assays and chromatin immunoprecipitation revealed that Sp1 and Sp3 bound specifically to the most proximal GC-site. Furthermore, we showed that Sp1 and Sp3 over-expression activates CD97 promoter activity in HEK 293 cells.Our data characterize for the first time the activity of the human CD97 promoter which is controlled by Sp1/Sp3 transcription factors in SMCs.2

show abstract

LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors

Cited by 171 publications

References 45 publications

N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding

N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding

Inactivation of the EGF‐TM7 receptor EMR4 after the Pan‐Homo divergence

Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle cells

Contact Info

Product

Resources

About