Journal article
Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo
The Journal of cell biology, Vol.130(2), pp.441-450
07/15/1995
DOI: 10.1083/jcb.130.2.441
PMCID: PMC2199943
PMID: 7542248
Abstract
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.
Details
- Title: Subtitle
- Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo
- Creators
- E J Filardo - Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USAP C Brooks - Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USAS L Deming - Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USAC Damsky - Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USAD A Cheresh - Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.130(2), pp.441-450
- DOI
- 10.1083/jcb.130.2.441
- PMID
- 7542248
- PMCID
- PMC2199943
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 07/15/1995
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Internal Medicine
- Record Identifier
- 9984051503602771
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