Highly stoichiometric, stable, and specific association of integrin α3β1 with CD151 provides a major link to phosphatidylinositol 4 kinase, and may regulate cell migration

Highly stoichiometric, stable, and specific association of integrin α3β1 with CD151 provides a major link to phosphatidylinositol 4 kinase, and may regulate cell migration
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DOI:
10.1091/mbc.9.10.2751
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发表时间:
1998-10-01
影响因子:
3.3
通讯作者:
Hemler, ME
Hemler, ME
中科院分区:
生物学3区
文献类型:
--
作者:
Yauch, RL;Berditchevski, F;Hemler, ME

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在这里,我们描述了α 3 β 1整合素和跨膜4超家族(TM 4SF)蛋白CD 151之间的关联。这种关联在相对严格的洗涤剂中得以维持,因此与先前报道的整合素-TM 4SF蛋白关联相比非常稳定。此外,该关联是高度特异性的(即,在没有任何其它细胞表面蛋白的情况下在体外观察到),和高度化学计量(接近90%的α 3 β 1与CD 151相关)。此外,α 3 β 1和CD 151在许多细胞系上平行出现,并显示出几乎相同的皮肤染色模式。与其他整合素相比,α 3 β 1表现出相当高水平的相关磷脂酰肌醇-4-激酶(PtdIns 4-激酶)活性,其中大部分在CD 151免疫耗竭后被去除。CD 151和PtdIns 4-激酶关联的特异性位于α 3 β 1的细胞外结构域,从而建立了细胞内信号分子特异性募集的新范例。最后,针对CD 151或α 3 β 1的抗体响应于纤连蛋白上的f-Met-Leu-Phe引起中性粒细胞运动性的类似88-92%的降低,表明这些复合物在细胞迁移中的功能重要作用。
Here we describe an association between alpha 3 beta 1 integrin and transmembrane-4 superfamily (TM4SF) protein CD151. This association is maintained in relatively stringent detergents and thus is remarkably stable in comparison with previously reported integrin-TM4SF protein associations. Also, the association is highly specific (i.e., observed in vitro in absence of any other cell surface proteins), and highly stoichiometric (nearly 90% of alpha 3 beta 1 associated with CD151). In addition, alpha 3 beta 1 and CD151 appeared in parallel on many cell lines and showed nearly identical skin staining patterns. Compared with other integrins, alpha 3 beta 1 exhibited a considerably higher level of associated phosphatidylinositol-4-kinase (PtdIns 4-kinase) activity, most of which was removed upon immunodepletion of CD151. Specificity for CD151 and PtdIns 4-kinase association resided in the extracellular domain of alpha 3 beta 1, thus establishing a novel paradigm for the specific recruitment of an intracellular signaling molecule. Finally, antibodies to either CD151 or alpha 3 beta 1 caused a similar to 88-92% reduction in neutrophil motility in response to f-Met-Leu-Phe on fibronectin, suggesting an functionally important role of these complexes in cell migration.