Characterization of the metastasis-associated protein, S100A4 - Roles of calcium binding and dimerization in cellular localization and interaction with myosin

Kim, E. J., Helfman, D. M. (August 2003) Characterization of the metastasis-associated protein, S100A4 - Roles of calcium binding and dimerization in cellular localization and interaction with myosin. Journal of Biological Chemistry, 278 (32). pp. 30063-30073. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/12756252
DOI: 10.1074/jbc.M304909200

Abstract

Elevated S100A4 protein expression is associated with metastatic tumor progression and appears to be a strong molecular marker for clinical prognosis. S100A4 is a calcium-binding protein that is known to form homodimers and interacts with several proteins in a calcium-dependent manner. Here we show that S100A4 localizes to lamellipodia structures in a migrating breast cancer-derived cell line and colocalizes with a known S100A4-interacting protein, myosin heavy chain IIA, at the leading edge. We demonstrate that S100A4 mutants that are defective in either their ability to dimerize or in calcium binding are unable to interact with myosin heavy chain IIA. An S100A4 mutant that is deficient for calcium binding retains the ability to form homodimers, suggesting that S100A4 can exist as calcium-free or calcium-bound dimers in vivo. However, a calcium-bound S100A4 monomer only interacts with another calcium-bound monomer and not with an S100A4 mutant that does not bind calcium. Interestingly, despite the calcium dependence for interaction with known protein partners, calcium binding is not necessary for localization to lamellipodia. Both wild type and a mutant that is deficient for calcium binding colocalize with known markers of actively forming leading edges of lamellipodia, Arp3 and neuronal Wiskott-Aldrich syndrome protein. These data suggest that S100A4 localizes to the leading edge in a calcium-independent manner, and identification of the proteins that are involved in localizing S100A4 to the lamellipodial structures may provide novel insight into the mechanism by which S100A4 regulates metastasis.

Item Type: Paper
Uncontrolled Keywords: HUMAN BREAST-CANCER NONMUSCLE MYOSIN PROGNOSTIC-SIGNIFICANCE TUMOR-CELLS HEAVY-CHAIN MTS1 PROTEIN IN-VIVO CA2+-BINDING PROTEINS CARCINOMA-CELLS PEL98 PROTEIN
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > calcium channel
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > myosin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Helfman lab
Depositing User: Matt Covey
Date: August 2003
Date Deposited: 27 Jun 2013 14:39
Last Modified: 27 Jun 2013 14:39
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27930

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