Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells.

Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells.
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DOI:
10.1083/jcb.132.1.211
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发表时间:
1996-01
影响因子:
7.8
通讯作者:
Burridge, K
Burridge, K
中科院分区:
生物学1区
文献类型:
--
作者:
Belkin, AM;Zhidkova, NI;Balzac, F;Altruda, F;Tomatis, D;Maier, A;Tarone, G;Koteliansky, VE;Burridge, K

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整合素的胞质结构域提供这些细胞外基质受体与细胞骨架的连接,并在整合素介导的信号转导中起关键作用。在这份报告中,我们描述了一种新形式的β 1整合素,称为β 1D的识别,表达,定位和初步的功能表征。该亚型含有50个氨基酸的独特的可变剪接胞质结构域,最后24个氨基酸由额外的外显子编码。在这24个氨基酸中,当与β 1A同种型相比时,11个是保守的,但13个是独特的(Zhidkova,N.一、A. M. Belkin和R.梅恩1995.生物化学、生物物理通信资源214:279-285;货车der Flier,A.,I.库伊克曼角Baudoin,R,货车der Neuf和A.索南伯格1995. FEBS Lett. 369:340-344)。使用针对β 1D整合素亚基的抗肽抗体,我们证明了β 1D亚型仅在骨骼肌和心肌中合成,而在横纹肌中通过免疫印迹检测到非常少量的β 1A。而β 1A不能检测到成人骨骼肌纤维和心肌细胞的免疫荧光,β 1D定位于两种细胞类型的肌膜。在骨骼肌中,β 1D集中在肋肌、肌腱和神经肌肉接头。在心肌中,这种β 1亚型存在于肋突和闰盘中。在成人骨骼肌中β 1D与α 7A和α 7 B相关。在成人心脏的心肌细胞中,α 7 B是β 1D亚型的主要伙伴。β 1D在增殖的C2 C12成肌细胞中不能检测到,但在成肌细胞融合后立即出现,并且在肌管生长和成熟过程中其量继续增加。相反,β 1A亚型的表达在培养的肌分化过程中下调,并且在成熟分化的肌管中完全被β 1D取代。我们还分析了β 1D整合素亚基的一些功能特性。人β 1D在CHO细胞中的表达导致其定位于粘着斑。这种整合素亚型在细胞表面上的聚集刺激pp 125 FAK(粘着斑激酶)的酪氨酸磷酸化,并引起促分裂原活化蛋白(MAP)激酶的瞬时活化。这些数据表明β 1D和β 1A整合素同种型在整合素介导的信号传导方面功能相似。
The cytoplasmic domains of integrins provide attachment of these extracellular matrix receptors to the cytoskeleton and play a critical role in integrin-mediated signal transduction. In this report we describe the identification, expression, localization, and initial functional characterization of a novel form of beta 1 integrin, termed beta 1D. This isoform contains a unique alternatively spliced cytoplasmic domain of 50 amino acids, with the last 24 amino acids encoded by an additional exon. Of these 24 amino acids, 11 are conserved when compared to the beta 1A isoform, but 13 are unique (Zhidkova, N. I., A. M. Belkin, and R. Mayne. 1995. Biochem. Biophys. Res. Commun. 214:279-285; van der Flier, A., I. Kuikman, C. Baudoin, R, van der Neuf, and A. Sonnenberg. 1995. FEBS Lett. 369:340-344). Using an anti-peptide antibody against the beta 1D integrin subunit, we demonstrated that the beta 1D isoform is synthesized only in skeletal and cardiac muscles, while very low amounts of beta 1A were detected by immunoblot in striated muscles. Whereas beta 1A could not be detected in adult skeletal muscle fibers and cardiomyocytes by immunofluorescence, beta 1D was localized to the sarcolemma of both cell types. In skeletal muscle, beta 1D was concentrated in costameres, myotendinous, and neuromuscular junctions. In cardiac muscle this beta 1 isoform was found in costamers and intercalated discs. beta 1D was associated with alpha 7A and alpha 7B in adult skeletal muscle. In cardiomyocytes of adult heart, alpha 7B was the major partner for the beta 1D isoform. beta 1D could not be detected in proliferating C2C12 myoblasts, but it appeared immediately after myoblast fusion and its amount continued to rise during myotube growth and maturation. In contrast, expression of the beta 1A isoform was downregulated during myodifferentiation in culture and it was completely displaced by beta 1D in mature differentiated myotubes. We also analyzed some functional properties of the beta 1D integrin subunit. Expression of human beta 1D in CHO cells led to its localization at focal adhesions. Clustering of this integrin isoform on the cell surface stimulated tyrosine phosphorylation of pp125FAK (focal adhesion kinase) and caused transient activation of mitogen-activated protein (MAP) kinases. These data indicate that beta 1D and beta 1A integrin isoforms are functionally similar with regard to integrin-mediated signaling.
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发表时间: 1993-08
期刊: The Journal of cell biology
影响因子: --
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期刊: NEURON
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DOI: 10.1083/jcb.121.1.171
发表时间: 1993-04
期刊: The Journal of cell biology
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发表时间: 1992-08-20
期刊: NATURE
影响因子: 64.8
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