Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
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人类淋巴细胞归巢受体 CD44 的多个变体通过插入胞外域的单个位点而产生。
DOI：
10.1016/s0021-9258(18)42893-1
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
J. Bell
中科院分区：
文献类型：
--
作者：
D. Jackson;J. Buckley;J. Bell
人 CD44+ 细胞表面糖蛋白参与多种细胞间相互作用，包括淋巴细胞归巢和肿瘤转移。已知 CD44 抗原在不同组织来源之间进行比较时表现出广泛的大小异质性，尽管这种变异的结构基础尚不清楚。最近，除了 CD44 抗原的基本造血形式之外，还克隆并测序了另外两种同种型，并发现它们在胞外域内含有全部或部分 200-400 碱基对插入，表明分子中的特征异质性可能是通过选择性剪接机制产生的。我们已经获得了选择性剪接的进一步证据，并且我们在这里报告了使用表达克隆和聚合酶链式反应的组合对来自多种细胞系的六种不同的 CD44 序列变体进行的克隆和测序。这些变体的比较表明，每个变体可能是通过将五个不同的外显子单元串联插入到胞外域的膜近端区域内的离散位点来组装的。其中一个变体包含一个外显子，该外显子与最近描述的介导肿瘤转移的大鼠 CD44 变体具有广泛的氨基酸序列同源性。另一种变体包含一个新的外显子，编码共有序列 SG 的串联重复，用于硫酸软骨素的共价修饰，并且主要在乳腺肿瘤上表达。我们认为，选择性外显子剪接机制产生了许多观察到的 CD44 结构异质性，并且在单个细胞中表达的特定 CD44 变体集可能代表了指导迁移细胞和转移性肿瘤最终目的地的精确邮政编码。
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.