Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo.
Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo.
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DOI：
10.1083/jcb.130.2.441
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发表时间：
1995-07
期刊：
影响因子：
--
通讯作者：
Cheresh DA
中科院分区：
文献类型：
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作者：
Filardo EJ;Brooks PC;Deming SL;Damsky C;Cheresh DA
NPXY序列在整联蛋白β亚基胞质尾区中高度保守，表明其在调节整联蛋白介导的功能中起重要作用。提供的证据表明，β 3亚基内的NPXY结构基序，包括残基744-747，是必不可少的细胞形态和迁移反应介导的整合素α v β 3在体外和体内。用编码野生型整联蛋白β 3亚基的cDNA转染CS-1黑色素瘤细胞，导致从头α v β 3表达和细胞在玻连蛋白上的附着、扩散和迁移。表达具有破坏NPXY序列的突变的α v β 3的CS-1细胞与可溶性玻连蛋白或RGD肽相互作用，但不能在固定化配体上附着、扩散或迁移。这些观察结果的生物学后果被以下发现所强调，即表达野生型α v β 3的CS-1细胞在鸡胚中在绒毛尿囊膜上生长时获得形成自发性肺转移的能力。然而，表达具有NPXY序列突变的α v β 3的迁移缺陷型CS-1细胞失去了这种转移能力。这些发现表明，整合素β 3胞质尾内的NPXY基序对于参与黑色素瘤细胞的细胞迁移和转移表型的α v β 3依赖性后配体结合事件是必需的。
The NPXY sequence is highly conserved among integrin beta subunit cytoplasmic tails, suggesting that it plays a fundamental role in regulating integrin-mediated function. Evidence is provided that the NPXY structural motif within the beta 3 subunit, comprising residues 744-747, is essential for cell morphological and migratory responses mediated by integrin alpha v beta 3 in vitro and in vivo. Transfection of CS-1 melanoma cells with a cDNA encoding the wild-type integrin beta 3 subunit, results in de novo alpha v beta 3 expression and cell attachment, spreading, and migration on vitronectin. CS-1 cells expressing alpha v beta 3 with mutations that disrupt the NPXY sequence interact with soluble vitronectin or an RGD peptide, yet fail to attach, spread, or migrate on immobilized ligand. The biological consequences of these observations are underscored by the finding that CS-1 cells expressing wild-type alpha v beta 3 acquire the capacity to form spontaneous pulmonary metastases in the chick embryo when grown on the chorioallantoic membrane. However, migration-deficient CS-1 cells expressing alpha v beta 3 with mutations in the NPXY sequence lose this ability to metastasize. These findings demonstrate that the NPXY motif within the integrin beta 3 cytoplasmic tail is essential for alpha v beta 3-dependent post-ligand binding events involved in cell migration and the metastatic phenotype of melanoma cells.