Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type-specific adhesion.
Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type-specific adhesion.
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鉴定人血浆纤连蛋白中介导细胞类型特异性粘附的剪接位点。
DOI：
10.1083/jcb.103.6.2637
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发表时间：
1986-12
影响因子：
7.8
通讯作者：
YAMADA, KM
中科院分区：
文献类型：
--
作者：
HUMPHRIES, MJ;AKIYAMA, SK;KOMORIYA, A;OLDEN, K;YAMADA, KM
我们比较了黑色素瘤和纤维母细胞与纤维连接蛋白的粘附相互作用的分子特异性。我们发现两种细胞类型对Arg-Gly-Asp-Ser （RGDS）四肽粘附信号抑制的敏感性存在显著差异。通过检测纤维连接蛋白水解片段的粘附性，获得了黑色素瘤和成纤维细胞粘附系统差异的进一步证据。成纤维细胞BHK细胞很容易在fl3上扩散，fl3是一个75-kD片段，代表含有rgds的纤维连接蛋白的“细胞结合”结构域，但B16-F10黑色素瘤细胞却不能。黑色素瘤细胞能够在f9上扩散，f9是一个来自纤维连接蛋白大亚基的113-kD片段，包含至少部分III型连接段差异区（或“V”区）；F7，来自小纤维连接蛋白亚基的片段缺乏这种选择性剪接多肽是无活性的。单克隆抗体和fl3抑制实验证实黑色素瘤细胞无法使用RGDS序列；这两种分子都不影响黑色素瘤细胞的扩散，但都完全消除了成纤维细胞的粘附。通过系统分析横跨整个III型连接段的一系列6个重叠的合成肽，在该区域COOH-末端附近的肽中发现了一个新的附着位点。与RGDS有一定关系的四肽序列Arg-Glu-Asp-Val （REDV）存在于III型连接段的高度亲水性区域。REDV似乎在功能上很重要，因为这种合成的四肽抑制黑色素瘤细胞对纤维连接蛋白的粘附，但对成纤维细胞的粘附无活性。因此，REDV代表了纤维连接蛋白中具有细胞类型特异性的新型粘附识别信号。这些结果表明，对于某些细胞类型，纤维连接蛋白促进粘附活性的调节可能通过mRNA的选择性剪接发生。
We have compared the molecular specificities of the adhesive interactions of melanoma and fibroblastic cells with fibronectin. Several striking differences were found in the sensitivity of the two cell types to inhibition by a series of synthetic peptides modeled on the Arg-Gly-Asp-Ser (RGDS) tetrapeptide adhesion signal. Further evidence for differences between the melanoma and fibroblastic cell adhesion systems was obtained by examining adhesion to proteolytic fragments of fibronectin. Fibroblastic BHK cells spread readily on fl3, a 75-kD fragment representing the RGDS-containing, "cell-binding" domain of fibronectin, but B16-F10 melanoma cells could not. The melanoma cells were able to spread instead on f9, a 113-kD fragment derived from the large subunit of fibronectin that contains at least part of the type III connecting segment difference region (or "V" region); f7, a fragment from the small fibronectin subunit that lacks this alternatively spliced polypeptide was inactive. Monoclonal antibody and fl3 inhibition experiments confirmed the inability of the melanoma cells to use the RGDS sequence; neither molecule affected melanoma cell spreading, but both completely abrogated fibroblast adhesion. By systematic analysis of a series of six overlapping synthetic peptides spanning the entire type III connecting segment, a novel attachment site was identified in a peptide near the COOH- terminus of this region. The tetrapeptide sequence Arg-Glu-Asp-Val (REDV), which is somewhat related to RGDS, was present in this peptide in a highly hydrophilic region of the type III connecting segment. REDV appeared to be functionally important, since this synthetic tetrapeptide was inhibitory for melanoma cell adhesion to fibronectin but was inactive for fibroblastic cell adhesion. REDV therefore represents a novel adhesive recognition signal in fibronectin that possesses cell type specificity. These results suggest that, for some cell types, regulation of the adhesion-promoting activity of fibronectin may occur by alternative mRNA splicing.
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DOI：
10.1038/newbio242148a0
发表时间：
1973-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
DOI：
10.1083/jcb.101.6.2134
发表时间：
1985-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Horwitz A;Duggan K;Greggs R;Decker C;Buck C
通讯作者：
Buck C
影响因子：
2.9
作者：
BERNARD, MP;KOLBE, M;CHU, ML
通讯作者：
CHU, ML
影响因子：
4
作者：
HASEGAWA, T;HASEGAWA, E;YAMADA, KM
通讯作者：
YAMADA, KM
生物活性合成肽作为胚胎发育的探针：纤连蛋白功能的竞争性肽抑制剂抑制两栖动物胚胎中的胃肠液和鸟类胚胎中神经rest细胞迁移。
影响因子：
7.8
作者：
Boucaut, J C;Darribere, T;Poole, T J;Aoyama, H;Yamada, K M;Thiery, J P
通讯作者：
Thiery, J P