Characterization of PINCH-2, a new focal adhesion protein that regulates the PINCH-1-ILK interaction, cell spreading, and migration.

Integrin-linked kinase (ILK) is a multidomain protein that plays important roles at cell-extracellular matrix (ECM) adhesion sites. We describe here a new LIM-domain containing protein (termed as PINCH-2) that forms a complex with ILK. PINCH-2 is co-expressed with PINCH-1 (previously known as PINCH), another member of the PINCH protein family, ...
in a variety of human cells. Immunofluorescent staining of cells with PINCH-2-specific antibodies show that PINCH-2 localizes to both cell-ECM contact sites and the nucleus. Deletion of the first LIM (LIM1) domain of PINCH-2 abolished the ability of PINCH-2 to form a complex with ILK. The ILK-binding defective LIM1-deletion mutant, unlike the wild type PINCH-2 or the ILK-binding competent LIM5-deletion mutant, was incapable of localizing to cell-ECM contact sites, suggesting that ILK binding is required for this process. Importantly, the PINCH-2-ILK and PINCH-1-ILK interactions are mutually exclusive. Overexpression of PINCH-2 significantly inhibited the PINCH-1-ILK interaction and reduced cell spreading and migration. These results identify a novel nuclear and focal adhesion protein that associates with ILK and reveals an important role of PINCH-2 in the regulation of the PINCH-1-ILK interaction, cell shape change, and migration.
Mesh Terms:
Animals, Carrier Proteins, Cell Adhesion, Cell Line, Cell Movement, Cell Size, DNA-Binding Proteins, Extracellular Matrix, Focal Adhesions, Genes, Reporter, Humans, Immunohistochemistry, Mice, Molecular Sequence Data, Nuclear Proteins, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins
J. Biol. Chem.
Date: Oct. 11, 2002
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