Evidence for an extended structure of the T-cell co-receptor CD8 alpha as deduced from the hydrodynamic properties of soluble forms of the extracellular region.

Boursier, Jean-Philippe; Alcover, Andrés; Herve, F; Laisney, I; Acuto, Oreste

doi:10.1016/s0021-9258(18)53956-9

Cited by 18 publications

(1 citation statement)

References 60 publications

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“…These results obtained from detailed biochemical analyses provide further evidence that the alternative exons constitute a mucin-like domain as predicted initially from their hydrophyllicity and from their high content of serine and threonine residues. Mucin-like regions in other leukocyte cell surface glycoproteins such as leukosialin (CD43) and the hinge region of the T cell molecule CD8 have been observed to adopt extended rod-like conformations in EM (Cyster et al, 1991) and hydrodynamic studies (Boursier et al, 1993). Indeed if the membraneproximal region within the CD44~3-~o isoform were to adopt the same conformation as the 224 residue mucin-like extracellular domain of CIM3 (length 45 nm under EM; Cyster et al, 1991), then the 340-amino acid v3-10 insert would increase the length of the extracellular domain by some 60 nm.…”

Section: Alternative Splicing Of Exons V4-vlo Generates Cd44 Molecules That Are Heavily O-glycosylatedmentioning

confidence: 99%

Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon.

Jackson

Bell

Dickinson

et al. 1995

The Journal of Cell Biology

238

163

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Abstract. The CD44 cell surface glycoprotein is expressed on a broad range of different tissues as multiple isoforms containing from one to ten alternatively spliced exons vl-vl0 inserted within the extracellular domain. Differential glycosylation generates still further variability, yielding both N-and O-glycanmodified forms of CD44 in addition to proteoglycanlike variants containing chondroitin sulphate and heparan sulphate. These high molecular mass proteoglycan-like variants, previously identified in lymphocytes, melanomas, and keratinocytes have been implicated in cell-matrix adhesion, cell motility, and invasiveness. More recently, monocyte CD44 molecules presumed to carry glycosaminoglycan chains were shown to bind the chemokine MIP-1/~ (Tanaka, Y., D. H. Adams, S. Hubscher, H. Hirano, U. Siebenlist, and S. Shaw. 1993. Nature (Lond.). 361:79-82.) raising the intriguing possibility that proteoglycan-like CD44 variants might play a role in regulating inflammatory responses.Here we have investigated the molecular identity of these proteoglycan-like CD44 variants by generating a panel of recombinant CD44 isoforms using a novel cassette cloning strategy. We show that both chondroitin and heparan sulphate modifications are associated specifically with isoforms (CD44v3-1o and CD44v3, containing the v3 alternative exon which encodes a consensus motif SGXG for GAG addition. Other isoforms (CD44v10, CD44vs-10, CD44v7-1o, and CD44,~-~o) are shown to lack these GAG chains but to carry extensive O-glycan modifications, most likely within the mucin-like alternative exon inserts. We also demonstrate that the majority of endogenous GAG-modified CD44 isoforms present in epithelial cells constitute v3 isoforms thus establishing that in these cells the majority of proteoglycan-like CD44 variants are generated by alternative splicing. Finally we present evidence using transfected B lymphoma cells that the GAG-modified CD44 isoforms CD44v3-10 and CD44~3,8-~0, unlike CD44H, bind only weakly to hyaluronan. Together with the demonstration in the accompanying paper (Bennett, K., D. G. Jackson, J. C. Simon, E. Tanczos, R. Peach, B. Modrell, I. Stamenkovic, G. Plowman, and A. Aruffo. 1995. J. Cell Biol. 128:687-698.), that CD44 molecules containing the v3 exon bind growth factors, these results highlight a new and potentially important role for CIM4 alternative splicing in the control of cell-surface proteoglycan expression.

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Section: Alternative Splicing Of Exons V4-vlo Generates Cd44 Molecules That Are Heavily O-glycosylatedmentioning

confidence: 99%

Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon.

Jackson

Bell

Dickinson

et al. 1995

The Journal of Cell Biology

238

163

View full text Add to dashboard Cite

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Cooperative Recognition of MHC Class II:Peptide Complexes by the T Cell Receptor and CD4

Vignali¹

1996

MHC Molecules: Expression, Assembly and Function

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Mechanisms of HIV-1 Nef Function and Intracellular Signaling

Foster¹,

Denial²,

Temple

et al. 2011

J Neuroimmune Pharmacol

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Advances in the last several years have enhanced mechanistic understanding of Nef induced CD4 and MHCI downregulation and have suggested a new paradigm for analyzing Nef function. In both of these cases, Nef acts by forming ternary complexes with significant contributions to stability imparted by non-canonical interactions. The mutational analyses and binding assays that have led to these conclusions are discussed. The recent progress has been dependent on conservative mutations and multi-protein binding assays. The poorly understood Nef functions of p21 activated protein kinase (PAK2) activation, enhancement of virion infectivity, and inhibition of immunoglobulin class switching are also likely to involve ternary complexes and non-canonical interactions. Hence, investigation of these latter Nef functions should benefit from a similar approach. Six historically used alanine substitutions for determining structure-function relationships of Nef are discussed. These are M20A, E62A/E63A/E64A/E65A (AAAA), P72A/P75A (AXXA), R106A, L164A/L165A, and D174A/D175A. Investigations of less disruptive mutations in place of AAAA and AXXA have led to different interpretations of mechanism. Two recent examples of this alternate approach applied to PAK2 activation F191 and critical residue D123 are presented. The implications of the new findings and the resulting new paradigm for Nef structure-function are discussed with respect to creating a map of Nef functions on the protein surface. We report the results of a PPI-Pred analysis for protein-protein interfaces. There are three predicted patches produced by the analysis which describe regions consistent with the currently known mutational analyses of Nef function.

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Evidence for an extended structure of the T-cell co-receptor CD8 alpha as deduced from the hydrodynamic properties of soluble forms of the extracellular region.

Cited by 18 publications

References 60 publications

Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon.

Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon.

Cooperative Recognition of MHC Class II:Peptide Complexes by the T Cell Receptor and CD4

Mechanisms of HIV-1 Nef Function and Intracellular Signaling

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