Detailed analysis of MIA protein by mutagenesis.
MIA (melanoma inhibitory activity) has been identified as a small protein secreted by malignant melanoma cells that interacts with extracellular matrix proteins including fibronectin. These findings suggest that MIA may play a role in tumor progression and the spread of malignant melanomas by mediating detachment of cells from extracellular matrix molecules. Here, we present a detailed study on functionally important MIA domains. Using site-directed mutagenesis, amino acids important for MIA structure and/or function were determined. Amino acids conserved in SH3 domains were shown to be important for structural integrity. In addition, amino acid residues necessary for MIA function were identified. Interestingly, not all of them are conserved with respect to other members of the MIA protein family. In summary, our results lead to a better understanding of MIA function. Regulating MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease.
Stoll
Raphael
R
University of Bochum, Faculty of Chemistry and Biochemistry, Biomolecular NMR, D-44780 Bochum, Germany.
Lodermeyer
Sibylla
S
Bosserhoff
Anja-Katrin
AK
D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins