Cloning, genomic organization, alternative transcripts and expression analysis of CD99L2 , a novel paralog of human CD99, and identification of evolutionary conserved motifs

Suh, Young Ho; Shin, Young Kee; Kook, Myeong Cherl; Oh, Kwon Ik; Park, Weon Seo; Kim, Seok Hyung; Lee, Im Soon; Park, Hyojin; Huh, Tae Lin; Park, Seong Hoe

doi:10.1016/s0378-1119(03)00401-3

Cited by 53 publications

(68 citation statements)

References 28 publications

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“…Although a number of studies have shown that CD99 interacts homophilically via its extracellular domain, the mechanisms involved are not clearly understood (25,49,50). CD99 includes three highly conserved regions in its extracellular domain across multiple species (51). We hypothesized that the conserved regions CD99CRI, -II, and -III are critical for the homophilic interaction of CD99.…”

Section: Discussionmentioning

confidence: 98%

CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway

Lee

Kim

Yoo

et al. 2017

Molecular and Cellular Biology

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The human CD99 protein is a 32-kDa glycosylated transmembrane protein that regulates various cellular responses, including cell adhesion and leukocyte extravasation. We previously reported that CD99 activation suppresses ␤1 integrin activity through dephosphorylation of focal adhesion kinase (FAK) at Y397. We explored a molecular mechanism underlying the suppression of ␤1 integrin activity by CD99 agonists and its relevance to tumor growth in vivo. CD99-Fc fusion proteins or a series of CD99-derived peptides suppressed ␤1 integrin activity by specifically interacting with three conserved motifs of the CD99 extracellular domain. CD99CRIII3, a representative CD99-derived 3-mer peptide, facilitated protein kinase A-SHP2 interaction and subsequent activation of the HRAS/RAF1/MEK/ERK signaling pathway. Subsequently, CD99CRIII3 induced FAK phosphorylation at S910, which led to the recruitment of PTPN12 and PIN1 to FAK, followed by FAK dephosphorylation at Y397. Taken together, these results indicate that CD99-derived agonist ligands inhibit fibronectin-mediated ␤1 integrin activation through the SHP2/ERK/PTPN12/FAK signaling pathway.

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Section: Discussionmentioning

confidence: 98%

CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway

Lee

Kim

Yoo

et al. 2017

Molecular and Cellular Biology

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“…This molecule is highly oglycosylated and together with Xga and CD99 L2 constitutes a family of molecules that show no homology to any other known family [21][22][23][24][25][26]. The mRNA of CD99 is expressed as two isoforms, a long form of 185 amino acids (CD99LF) and a short form of 161 amino acids (CD99SF) obtained by alternative splicing of the cytoplasmic region [27].…”

Section: Introductionmentioning

confidence: 99%

CD99 isoforms regulate CD1a expression in human monocyte‐derived DCs through ATF‐2/CREB‐1 phosphorylation

et al. 2016

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CD1a expression is considered one of the major characteristics qualifying in vitro human dendritic cells (DCs) during their generation process. Here, we report that CD1A transcription is regulated by a mechanism involving the long and short isoforms of CD99. Using a lentiviral construct encoding for a CD99 short hairpin RNA, we were able to inhibit CD99 expression in human primary DCs. In such cells, CD1a membrane expression increased and CD1A transcripts were much higher in abundance compared to cells expressing CD99 long form (CD99LF). We also show that CD1A transcription is accompanied by a switch in expression from CD99LF to expression at comparable levels of both CD99 isoforms during immature DCs generation in vitro. We demonstrate that CD99LF maintains a lower level of CD1A transcription by up-regulating the phosphorylated form of the ATF-2 transcription factor and that CD99 short form (SF) is required to counteract this regulatory mechanism. Elucidation of the molecular mechanisms related to CD99 alternative splicing will be very helpful to better understand the transcriptional regulatory mechanism of CD1a molecules during DCs differentiation and its involvement in the immune response.Keywords: alternative splicing-ATF2-CREB1 r CD99 r Dendritic cells r Nonclassical MHC Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionPresentation of foreign antigens in the form of proteins or lipids solicits specialized molecular complexes carried by dendritic cells (DCs). The molecules of the classical and nonclassical major Correspondence: Dr. Ghislaine Bernard e-mail: bernardg@unice.fr histocompatibility complex (MHC) class I present antigens to T cells and these two families of molecules have very similar structures [1][2][3].Among the nonclassical MHC molecules is the CD1 family of molecules that assures the presentation of lipid and glycolipid † Deceased C 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2016. 46: 1460-1471 Immunomodulation 1461 antigens [4,5]. This family consists of five genes, including CD1A, B, C, D and E. The first four give rise to cell surface proteins CD1a, CD1b, CD1c, CD1d that are able to present the antigens, while the gene CD1E codes for the cytoplasmic protein CD1e [6][7][8]. CD1a is expressed on the membranes of thymocytes, dermal DCs and Langerhans cells, and allows distinction between subpopulations of DCs. No such equivalent has been reported in mice [8].CD1a is expressed during generation of DCs derived from monocytes when cultured in the presence of GMCSF and IL4 in vitro [9]. Two subpopulations of immature DCs (iDCs), i.e. CD1a high and CD1a low DCs, are produced in these conditions [10,11]. In addition to their phenotypic differences, these cells show functional differences, in particular in terms of secretion of cytokines. In contrast to CD1a high DCs, CD1a low DCs produce low amounts of IL12 but produce high amounts of IL10. This profile of cytokines impacts on the f...

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“…CD99 exhibits 48% and 47% of sequence homology with two other proteins, Xg and mouse CD99L2, respectively, whose genes are located on the X chromosome (21,22). Xg is a 26-kDa molecule, whose gene which is located on/at the pseudoautosomal boundary of the short arm of the X chromosome (Xp22), in the vicinity of the CD99 gene (21,23).…”

Section: Introductionmentioning

confidence: 99%

“…The gene of CD99L2 (40 kDa) is located at the end of the long arm of the X chromosome (Xq28; ref. 22). From a structural viewpoint, CD99, Xg, and CD99L2 present four highly conserved regions including the FXLXDAL motif (in which X is any amino acid) and a glycine-rich region on the extracytoplasmic domain, the transmembrane domain.…”

Section: Introductionmentioning

confidence: 99%

“…From a structural viewpoint, CD99, Xg, and CD99L2 present four highly conserved regions including the FXLXDAL motif (in which X is any amino acid) and a glycine-rich region on the extracytoplasmic domain, the transmembrane domain. The fourth domain is the juxtamembrane region that is composed of positively charged lysine and arginine residues (22). CD99 and Xg also present a supplemental highly conserved domain that is a proline-rich region.…”

Section: Introductionmentioning

confidence: 99%

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Xg Expression in Ewing's Sarcoma Is of Prognostic Value and Contributes to Tumor Invasiveness

Meynet¹,

Scotlandi

Pradelli³

et al. 2010

Cancer Research

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Ewing's sarcoma (EWS) is an aggressive tumor of children and young adults that requires intensive treatment. The search for new prognostic factors is very important to choose the most appropriate therapy and to better understand the biology of the disease for the development of new therapeutic tools. We found that Xg, a thus far poorly described molecule and member of the CD99 family, is expressed in EWS cell lines and EWS primary tumors. Immunohistochemical analysis confirmed the expression of Xg in 24% of patients. We found that Xg expression in EWS defines a subgroup of patients with worse prognosis compared with those with Xgnegative localized tumors, indicating a clinical relevance of Xg expression in EWS. Forced expression of Xg in an EWS cell line upregulated cell migration and invasion in vitro. Furthermore, knockdown of Xg expression with specific short hairpin RNA significantly reduced migration and invasion of EWS cells. Consistent with these data, in vivo xenotransplant studies in nude mice revealed that Xg expression increased the incidence and the number of metastases of EWS cells. Thus, Xg expression is associated with lower overall survival in EWS patients with localized tumors and is implicated in metastasis. Cancer Res; 70(9); 3730-8. ©2010 AACR.

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Cloning, genomic organization, alternative transcripts and expression analysis of CD99L2 , a novel paralog of human CD99, and identification of evolutionary conserved motifs

Cited by 53 publications

References 28 publications

CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway

CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway

CD99 isoforms regulate CD1a expression in human monocyte‐derived DCs through ATF‐2/CREB‐1 phosphorylation

Xg Expression in Ewing's Sarcoma Is of Prognostic Value and Contributes to Tumor Invasiveness

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