Abstract
The Lasp-1 gene, which has been localized to the q12-q21 region of human chromosome 17, is amplified and overexpressed in human breast cancers. In addition to the previously reported LIM and SH3 domains of Lasp-1, we report here the identification of an actin-binding domain in the core of the protein. This domain is functional as we demonstrate that Lasp-1 binds actin in vivo and in vitro. In addition, confocal analysis of the Lasp-1 subcellular distribution shows that the protein is colocalized with actin at peripheral cell extensions in individual epithelial cancer cells and in transformed fibroblastic cells. Moreover, Lasp-1 is tyrosine phosphorylated in fibroblast cell lines transformed by a constitutively active form of c-Src (c-SrcY527F). Altogether, our results show that Lasp-1 defines a new type of actin-binding protein and suggest that the protein may play a role in a signaling pathway involved in the organization of the cytoskeleton.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Actins / metabolism
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Binding Sites
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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COS Cells
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Cell Membrane / metabolism
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Cell Transformation, Neoplastic
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Cytoskeletal Proteins
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Female
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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LIM Domain Proteins
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Mice
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Molecular Sequence Data
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Neoplasm Proteins*
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Phosphorylation
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Proto-Oncogene Proteins pp60(c-src) / genetics
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Subcellular Fractions
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Tumor Cells, Cultured
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Tyrosine / metabolism
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src Homology Domains* / genetics
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Cytoskeletal Proteins
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Homeodomain Proteins
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LASP1 protein, human
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LIM Domain Proteins
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Lasp1 protein, mouse
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Microfilament Proteins
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Neoplasm Proteins
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Tyrosine
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Proto-Oncogene Proteins pp60(c-src)