Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.

The human CD44 cell-surface glycoprotein participates in a wide variety of cell-cell interactions including lymphocyte homing and tumor metastasis. The CD44 antigen is known to display extensive size heterogeneity when compared between different tissue sources although the structural basis for this...

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Main Authors: Jackson, D, Buckley, J, Bell, J
Format: Journal article
Language:English
Published: 1992
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author Jackson, D
Buckley, J
Bell, J
author_facet Jackson, D
Buckley, J
Bell, J
author_sort Jackson, D
collection OXFORD
description The human CD44 cell-surface glycoprotein participates in a wide variety of cell-cell interactions including lymphocyte homing and tumor metastasis. The CD44 antigen is known to display extensive size heterogeneity when compared between different tissue sources although the structural basis for this variation is not yet clear. Recently, two further isotypes in addition to the basic hemopoietic form of the CD44 antigen have been cloned and sequenced and these have been found to contain all or part of a 200-400-base pair insert within the extracellular domain, suggesting that the characteristic heterogeneity in the molecule may be generated by a mechanism of alternative splicing. We have obtained further evidence for alternative splicing, and we report here the cloning and sequencing of six different CD44 sequence variants from a variety of cell lines using a combination of expression cloning and the polymerase chain reaction. Comparison of these variants indicates that each is probably assembled by the insertion of five different exon units in tandem into a discrete site within the membrane proximal region of the extracellular domain. One of the variants contains an exon that shares extensive amino acid sequence homology with a recently described rat CD44 variant that mediates tumor metastasis. Another variant contains a new exon that encodes a tandem repeat of the consensus sequence SG for covalent modification with chondroitin sulfate and is expressed predominantly on mammary tumors. We suggest that a mechanism of alternative exon splicing generates much of the observed structural heterogeneity of CD44 and that the particular set of CD44 variants expressed in a single cell may represent a precise postal code directing the final destination of migrating cells and metastatic tumors.
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spelling oxford-uuid:06fb46a1-f00b-4035-9fb7-7538b7bdbeb02022-03-26T09:05:11ZMultiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:06fb46a1-f00b-4035-9fb7-7538b7bdbeb0EnglishSymplectic Elements at Oxford1992Jackson, DBuckley, JBell, JThe human CD44 cell-surface glycoprotein participates in a wide variety of cell-cell interactions including lymphocyte homing and tumor metastasis. The CD44 antigen is known to display extensive size heterogeneity when compared between different tissue sources although the structural basis for this variation is not yet clear. Recently, two further isotypes in addition to the basic hemopoietic form of the CD44 antigen have been cloned and sequenced and these have been found to contain all or part of a 200-400-base pair insert within the extracellular domain, suggesting that the characteristic heterogeneity in the molecule may be generated by a mechanism of alternative splicing. We have obtained further evidence for alternative splicing, and we report here the cloning and sequencing of six different CD44 sequence variants from a variety of cell lines using a combination of expression cloning and the polymerase chain reaction. Comparison of these variants indicates that each is probably assembled by the insertion of five different exon units in tandem into a discrete site within the membrane proximal region of the extracellular domain. One of the variants contains an exon that shares extensive amino acid sequence homology with a recently described rat CD44 variant that mediates tumor metastasis. Another variant contains a new exon that encodes a tandem repeat of the consensus sequence SG for covalent modification with chondroitin sulfate and is expressed predominantly on mammary tumors. We suggest that a mechanism of alternative exon splicing generates much of the observed structural heterogeneity of CD44 and that the particular set of CD44 variants expressed in a single cell may represent a precise postal code directing the final destination of migrating cells and metastatic tumors.
spellingShingle Jackson, D
Buckley, J
Bell, J
Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
title Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
title_full Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
title_fullStr Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
title_full_unstemmed Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
title_short Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
title_sort multiple variants of the human lymphocyte homing receptor cd44 generated by insertions at a single site in the extracellular domain
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