整合素β1亚基的点突变可阻断α5β1与纤连蛋白和侵袭素的结合，但不影响其向黏着斑的募集。
A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.
作者信息
Takada Y, Ylänne J, Mandelman D, Puzon W, Ginsberg M H
机构信息
Committee on Vascular Biology, Scripps Research Institute, La Jolla, CA 92037.
出版信息
J Cell Biol. 1992 Nov;119(4):913-21. doi: 10.1083/jcb.119.4.913.
Abstract
A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus defining a dominant negative beta 1 integrin mutation.
摘要
β1亚基高度保守区域的一个点突变，即天冬氨酸130突变为丙氨酸（D130A）取代，消除了α5β1与纤连蛋白（FN）的精氨酸 - 甘氨酸 - 天冬氨酸（RGD）依赖性结合，而不破坏总体结构或异二聚体组装。D130A突变也干扰了与侵袭素（一种缺乏RGD序列的配体）的结合。尽管α5β1（D130A）无法检测到与FN的结合，但它被内源性仓鼠受体募集到在FN上形成的粘着斑。因此，将α5β1募集到粘着斑并不需要完整的配体结合功能。β1（D130A）的过表达部分干扰了内源性α5β1的功能，从而确定了一种显性负性β1整合素突变。
相似文献
1
A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.整合素β1亚基的点突变可阻断α5β1与纤连蛋白和侵袭素的结合，但不影响其向黏着斑的募集。
J Cell Biol. 1992 Nov;119(4):913-21. doi: 10.1083/jcb.119.4.913.
2
Molecular basis of ligand recognition by integrin alpha 5beta 1. I. Specificity of ligand binding is determined by amino acid sequences in the second and third NH2-terminal repeats of the alpha subunit.整联蛋白α5β1对配体识别的分子基础。I. 配体结合的特异性由α亚基氨基末端第二和第三个重复序列中的氨基酸序列决定。
J Biol Chem. 2000 Jul 7;275(27):20324-36. doi: 10.1074/jbc.M000572200.
3
Fine mapping of inhibitory anti-alpha5 monoclonal antibody epitopes that differentially affect integrin-ligand binding.对抑制性抗α5单克隆抗体表位进行精细定位，这些表位对整合素-配体结合有不同影响。
Biochem J. 1999 Dec 1;344 Pt 2(Pt 2):527-33.
4
5
Substrate-specific binding of the amino terminus of fibronectin to an integrin complex in focal adhesions.纤连蛋白氨基末端与粘着斑中整合素复合物的底物特异性结合。
J Biol Chem. 1994 Jul 29;269(30):19646-52.
6
The alpha v beta 1 integrin functions as a fibronectin receptor but does not support fibronectin matrix assembly and cell migration on fibronectin.αvβ1整合素作为纤连蛋白受体发挥作用，但不支持纤连蛋白基质组装以及细胞在纤连蛋白上的迁移。
J Cell Biol. 1993 Jul;122(1):235-42. doi: 10.1083/jcb.122.1.235.
7
A point mutation in the integrin beta 6 subunit abolishes both alpha v beta 6 binding to fibronectin and receptor localization to focal contacts.整联蛋白β6亚基中的一个点突变既消除了αvβ6与纤连蛋白的结合，也消除了受体在粘着斑处的定位。
Am J Respir Cell Mol Biol. 1995 Aug;13(2):245-51. doi: 10.1165/ajrcmb.13.2.7626292.
8
Possible involvement of the interaction of the alpha 5 subunit of alpha 5 beta 1 integrin with the synergistic region of the central cell-binding domain of fibronectin in cells to fibronectin binding.α5β1整合素的α5亚基与纤连蛋白中央细胞结合域的协同区域之间的相互作用可能参与细胞与纤连蛋白的结合。
Exp Cell Res. 1995 Jan;216(1):273-6. doi: 10.1006/excr.1995.1033.
9
Activation of the alpha 4 beta 1 integrin through the beta 1 subunit induces recognition of the RGDS sequence in fibronectin.通过β1亚基激活α4β1整合素可诱导对纤连蛋白中RGDS序列的识别。
J Cell Biol. 1994 Jul;126(1):271-9. doi: 10.1083/jcb.126.1.271.
10
Molecular basis of ligand recognition by integrin alpha5beta 1. II. Specificity of arg-gly-Asp binding is determined by Trp157 OF THE alpha subunit.整合素α5β1对配体识别的分子基础。II. α亚基的色氨酸157决定精氨酸-甘氨酸-天冬氨酸结合的特异性。
J Biol Chem. 2000 Jul 7;275(27):20337-45. doi: 10.1074/jbc.M000568200.
引用本文的文献
1
Expression of integrins to control migration direction of electrotaxis.整合素表达控制电趋性迁移方向。
FASEB J. 2019 Aug;33(8):9131-9141. doi: 10.1096/fj.201802657R. Epub 2019 May 22.
2
ADAM8 localizes to extravillous trophoblasts within the maternal-fetal interface and potentiates trophoblast cell line migration through a β1 integrin-mediated mechanism.ADAM8 定位于母胎界面的绒毛外滋养细胞中，并通过β1 整合素介导的机制增强滋养细胞系的迁移。
Mol Hum Reprod. 2018 Oct 1;24(10):495-509. doi: 10.1093/molehr/gay034.
3
Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition.通过整合素受体竞争抑制轮状病毒感染的马乳黏附素衍生肽的鉴定
J Biol Chem. 2015 May 8;290(19):12403-14. doi: 10.1074/jbc.M114.620500. Epub 2015 Mar 26.
4
The interaction between uPAR and vitronectin triggers ligand-independent adhesion signalling by integrins.uPAR 与 vitronectin 的相互作用触发整合素的配体非依赖性黏附信号转导。
EMBO J. 2014 Nov 3;33(21):2458-72. doi: 10.15252/embj.201387611. Epub 2014 Aug 28.
5
The primacy of β1 integrin activation in the metastatic cascade.β1 整合素激活在转移级联中的首要地位。
PLoS One. 2012;7(10):e46576. doi: 10.1371/journal.pone.0046576. Epub 2012 Oct 3.
6
Monkey rotavirus binding to alpha2beta1 integrin requires the alpha2 I domain and is facilitated by the homologous beta1 subunit.猴轮状病毒与α2β1整合素的结合需要α2结构域，并由同源的β1亚基促进。
J Virol. 2003 Sep;77(17):9486-501. doi: 10.1128/jvi.77.17.9486-9501.2003.
7
Differential role of beta(1C) and beta(1A) integrin cytoplasmic variants in modulating focal adhesion kinase, protein kinase B/AKT, and Ras/Mitogen-activated protein kinase pathways.β(1C)和β(1A)整合素细胞质变体在调节粘着斑激酶、蛋白激酶B/AKT和Ras/丝裂原活化蛋白激酶途径中的差异作用。
Mol Biol Cell. 2000 Jul;11(7):2235-49. doi: 10.1091/mbc.11.7.2235.
8
ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism.ADAM 23/MDC3，一种人去整合素，通过一种不依赖RGD的机制与αvβ3整合素相互作用来促进细胞黏附。
Mol Biol Cell. 2000 Apr;11(4):1457-69. doi: 10.1091/mbc.11.4.1457.
9
beta1 integrins regulate keratinocyte adhesion and differentiation by distinct mechanisms.β1整合素通过不同机制调节角质形成细胞的黏附与分化。
Mol Biol Cell. 2000 Feb;11(2):453-66. doi: 10.1091/mbc.11.2.453.
10
Defining extracellular integrin alpha-chain sites that affect cell adhesion and adhesion strengthening without altering soluble ligand binding.确定影响细胞黏附及黏附增强而不改变可溶性配体结合的细胞外整合素α链位点。
Mol Biol Cell. 1997 Dec;8(12):2647-57. doi: 10.1091/mbc.8.12.2647.
本文引用的文献
1
Expression of the mouse dihydrofolate reductase complementary deoxyribonucleic acid in simian virus 40 vectors.小鼠二氢叶酸还原酶互补脱氧核糖核酸在猿猴病毒40载体中的表达。
Mol Cell Biol. 1981 Sep;1(9):854-64. doi: 10.1128/mcb.1.9.854-864.1981.
2
The cell attachment domain of fibronectin. Determination of the primary structure.纤连蛋白的细胞附着结构域。一级结构的测定。
J Biol Chem. 1982 Aug 25;257(16):9593-7.
3
Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity.缺乏二氢叶酸还原酶活性的中国仓鼠细胞突变体的分离
Proc Natl Acad Sci U S A. 1980 Jul;77(7):4216-20. doi: 10.1073/pnas.77.7.4216.
4
Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA.使用M13衍生载体的寡核苷酸定向诱变：在任何DNA片段中产生点突变的高效通用方法。
Nucleic Acids Res. 1982 Oct 25;10(20):6487-500. doi: 10.1093/nar/10.20.6487.
5
Amplification and expression of sequences cotransfected with a modular dihydrofolate reductase complementary dna gene.与模块化二氢叶酸还原酶互补DNA基因共转染的序列的扩增与表达。
J Mol Biol. 1982 Aug 25;159(4):601-21. doi: 10.1016/0022-2836(82)90103-6.
6
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.在噬菌体T4头部组装过程中结构蛋白的切割
Nature. 1970 Aug 15;227(5259):680-5. doi: 10.1038/227680a0.
7
Selective inhibition of fibronectin-mediated cell adhesion by monoclonal antibodies to a cell-surface glycoprotein.针对一种细胞表面糖蛋白的单克隆抗体对纤连蛋白介导的细胞黏附的选择性抑制作用。
Science. 1985 Jun 21;228(4706):1448-51. doi: 10.1126/science.4012302.
8
Characterization of the cell surface heterodimer VLA-4 and related peptides.细胞表面异二聚体VLA - 4及相关肽的表征
J Biol Chem. 1987 Aug 25;262(24):11478-85.
9
Rapid and efficient site-specific mutagenesis without phenotypic selection.无需表型选择的快速高效位点特异性诱变。
Methods Enzymol. 1987;154:367-82. doi: 10.1016/0076-6879(87)54085-x.
10
Site-directed mutagenesis of the cell-binding domain of human fibronectin: separable, synergistic sites mediate adhesive function.人纤连蛋白细胞结合结构域的定点诱变：可分离的协同位点介导黏附功能。
Cell. 1988 May 20;53(4):649-57. doi: 10.1016/0092-8674(88)90580-6.
Zotero 插件