Protein sequence and gene structure for mouse leukosialin (CD43), a T lymphocyte mucin without introns in the coding sequence

Cyster, Jason G.; Somoza, Chamorro; Killeen, Nigel; Williams, Alan F.

doi:10.1002/eji.1830200424

Cited by 61 publications

(27 citation statements)

References 43 publications

(24 reference statements)

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“…DNA sequence comparison of rat, human, and mouse CD43 genes reveals that the transmembrane and intracellular domains are highly conserved compared to the extracellular portion, indicating differential selective pressures on either end of this protein (6)(7)(8)(9)(10)(11)(12) …”

Section: Introductionmentioning

confidence: 99%

Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.

Dragone

Barth

Sitar

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 Leukosialin [also designated as CD43, sialophorin and large sialoglycoprotein in humans, Ly48 or mouse CD43 (mCD43) in mice, and W3/13 in rats] is a major cell surface sialoglycoprotein found on T cells, granulocytes, macrophages, and both erythroid and B cells at specific stages of development (1). Altered expression of this molecule has been associated with the X chromosome-linked immunodeficiency disease Wiskott-Aldrich syndrome (2-4). Further interest in CD43 has been generated by the finding that anti-CD43 antibodies are present in AIDS patients, leading to speculation that these antibodies might contribute to human immunodeficiency virus-mediated immunodeficiency (5).The reported association of CD43 with specific immunodeficiency diseases and the unusual structural features of this molecule have fueled speculations regarding its function.CD43 has an extracellular domain that is highly 0-glycosylated, with carbohydrates making up >50% of its mass, and a relatively long intracellular domain (6, 7). DNA sequence comparison of rat, human, and mouse CD43 genes reveals that the transmembrane and intracellular domains are highly conserved compared to the extracellular portion, indicating differential selective pressures on either end of this protein (6)(7)(8)(9)(10)(11)(12)

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Section: Introductionmentioning

confidence: 99%

Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.

Dragone

Barth

Sitar

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…This abundant glycoprotein seems to play multiple roles in regulating leukocyte migration and activation. Due to its extended structure that protrudes 45 nm from the cell surface and its highly glycosylated nature (16), it has been proposed that CD43 constitutes a functional barrier that negatively affects T cell interactions and functions. Lymphocytes from CD43-deficient mice were reported to have enhanced rolling and adhesion in response to chemotactic stimuli, as well as increased in vitro proliferation (17)(18)(19).…”

mentioning

confidence: 99%

The CD43 Coreceptor Molecule Recruits the ζ-Chain as Part of Its Signaling Pathway

Cruz-Muñoz

Salas‐Vidal

Salaiza‐Suazo

et al. 2003

The Journal of Immunology

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CD43 is an abundant cell surface sialoglycoprotein implicated in hemopoietic cell adhesion and activation. Cell stimulation through CD43 results in recruitment of different signaling proteins, including members of the Src family kinases, Syk, phospholipase Cγ2, the adapter protein Shc, the guanine nucleotide exchange factor Vav, and activation of protein kinase C. In this study, we report that in human T lymphocytes, the ζ-chain is part of the CD43 signaling pathway. Upon CD43 engagement, the ζ-chain was tyrosine-phosphorylated, generating docking sites for tyrosine-phosphorylated ζ-associated protein of 70 kDa and Vav. In vitro kinase assays suggested that ζ-associated protein of 70 kDa could account for the kinase activity associated with the ζ-chain following CD43 engagement. Cross-linking CD43 on the surface of the Lck-deficient JCaM.1 cells failed to phosphorylate the ζ-chain and associated proteins, suggesting that Lck is a key element in the CD43 signaling pathway leading to ζ phosphorylation. CD43 engagement with beads coated with anti-CD43 mAb resulted in concentration of the ζ-chain toward the bead attachment site, but interestingly, the distribution of the T cell Ag receptor complex remained unaffected. Recruitment of the ζ-chain through CD43-mediated signals was not restricted to T lymphocytes because phosphorylation and redistribution of the ζ-chain was also observed in NK cells. Our results provide evidence that the ζ-chain functions as a scaffold molecule in the CD43 signaling pathway, favoring the recruitment and formation of downstream signaling complexes involved in the CD43-mediated cell activation of T lymphocytes and other leukocytes such as NK cells.

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“…The extracellular domain of CD43 is highly glycosylated and sialylated. This results in a negatively charged, rigid molecule, making CD43 an ideal candidate for nonspecific inhibition of protein-protein interactions at the cell surface (10,11). CD43-deficient cells are more responsive to Ag and are hyperadhesive, presumably due the reduced steric hindrance in the absence of the extracellular domain of CD43 (Refs.…”

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confidence: 99%

Polar Redistribution of the Sialoglycoprotein CD43: Implications for T Cell Function

Savage¹,

Kimzey²,

Bromley

et al. 2002

The Journal of Immunology

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Contact between T cells and APCs results in the orchestrated segregation of molecules at the cell-cell interface and formation of a specialized structure termed the immunological synapse. This model predicts the topological seclusion of large molecules such as CD43 from the site of closest contact between the T cell and APC, allowing for the close apposition of cell membranes and effective TCR engagement. Similarly, during T cell migration segregation of CD43 to the uropod is thought to aid integrin adhesion at the leading edge of the cell by removing steric hindrance. We show in this work that CD43 distribution on T cells is regulated by a membrane proximal ezrin binding site and that failure to displace CD43 from the immunological synapse has no inhibitory effects on primary T cell activation. We also report that CD43 expression at the contact zone between T cells and matrix does not negatively regulate motility but may regulate LFA-1 de-adhesion. These results suggest that the steric barrier model of CD43 is inadequate and that alternative mechanisms account for the negative regulatory properties of CD43.

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Protein sequence and gene structure for mouse leukosialin (CD43), a T lymphocyte mucin without introns in the coding sequence

Cited by 61 publications

References 43 publications

Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.

Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.

The CD43 Coreceptor Molecule Recruits the ζ-Chain as Part of Its Signaling Pathway

Polar Redistribution of the Sialoglycoprotein CD43: Implications for T Cell Function

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