Detailed analysis of MIA protein by mutagenesis
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Raphael Stoll
Abstract
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.
References
Blesch, A., Bosserhoff, A.K., Apfel, R., Behl, C., Hessdoerfer, B., Schmitt, A., Jachimczak, P., Lottspeich, F., Buettner, R., and Bogdahn, U. (1994). Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA. Cancer Res.54, 5695–5701.Search in Google Scholar
Bosserhoff, A.K., Hein, R., Bogdahn, U., and Buettner, R. (1996). Structure and promoter analysis of the gene encoding the human melanoma-inhibiting protein MIA. J. Biol. Chem.271, 490–495.10.1074/jbc.271.1.490Search in Google Scholar
Bosserhoff, A.K., Kaufmann, M., Kaluza, B., Bartke, I., Zirngibl, H., Hein, R., Stolz, W., and Buettner, R. (1997). Melanoma-inhibiting activity, a novel serum marker for progression of malignant melanoma. Cancer Res.57, 3149–3153.Search in Google Scholar
Bosserhoff, A.K., Echtenacher, B., Hein, R., and Buettner, R. (2001). Functional role of melanoma inhibitory activity in regulating invasion and metastasis of malignant melanoma cells in vivo. Melanoma Res.11, 417–421.10.1097/00008390-200108000-00013Search in Google Scholar
Bosserhoff, A.K., Stoll, R., Sleeman, J.P., Bataille, F., Buettner, R., and Holak, T.A. (2003). Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity. Lab. Invest.83, 1583–1594.10.1097/01.LAB.0000097191.12477.5DSearch in Google Scholar
Dalgarno, D.C., Botfield, M.C., and Rickles, R.J. (1997). SH3 domains and drug design: ligands, structure, and biological function. Biopolymers43, 383–400.10.1002/(SICI)1097-0282(1997)43:5<383::AID-BIP4>3.0.CO;2-RSearch in Google Scholar
Guba, M., Bosserhoff, A.K., Steinbauer, M., Abels, C., Anthuber, M., Buettner, R., and Jauch, K.W. (2000). Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo. Br. J. Cancer83, 1216–1222.10.1054/bjoc.2000.1424Search in Google Scholar
Jacob, K., Bosserhoff, A.K., Wach, F., Knuchel, R., Klein, E.C., Hein, R., and Buettner, R. (1995). Characterization of selected strongly and weakly invasive sublines of a primary human melanoma cell line and isolation of subtractive cDNA clones. Int. J. Cancer60, 668–675.10.1002/ijc.2910600517Search in Google Scholar
Kay, L.E. (1998). Protein dynamics from NMR. Biochem. Cell Biol.76, 145–152.10.1139/o98-024Search in Google Scholar
Lougheed, J.C., Holton, J.M., Alber, T., Bazan, J.F., and Handel, T.M. (2001). Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins. Proc. Natl. Acad. Sci. USA98, 5515–5520.10.1073/pnas.091601698Search in Google Scholar
Musacchio, A., Saraste, M., and Wilmanns, M. (1994). High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides. Nat. Struct. Biol.1, 546–551.10.1038/nsb0894-546Search in Google Scholar
Renner, C. and Holak, T. (2001). NMR 15N relaxation of the insulin-like growth factor (IGF)-binding domain of IGF binding protein-5 (IGFBP-5) determined free in solution and in complex with IGF-II. Eur. J. Biochem.268, 1058–1065.10.1046/j.1432-1327.2001.01965.xSearch in Google Scholar
Rothhammer, T., Poser, I., Soncin, F., Bataille, F., Moser, M., and Bosserhoff, A.K. (2005). Bone morphogenic proteins are overexpressed in malignant melanoma and promote cell invasion and migration. Cancer Res.65, 448–456.10.1158/0008-5472.448.65.2Search in Google Scholar
Stoll, R., Renner, C., Ambrosius, D., Golob, M., Voelter, W., Buettner, R., Bosserhoff, A.K., and Holak, T.A. (2000). Sequence-specific 1H, 13C, and 15N assignment of the human melanoma inhibitory activity (MIA) protein. J. Biomol. NMR17, 87–88.10.1023/A:1008306918293Search in Google Scholar
Stoll, R., Renner, C., Zweckstetter, M., Bruggert, M., Ambrosius, D., Palme, S., Engh, R.A., Golob, M., Breibach, I., Buettner, R., et al. (2001). The extracellular human melanoma inhibitory activity (MIA) protein adopts an SH3 domain-like fold. EMBO J.20, 340–349.10.1093/emboj/20.3.340Search in Google Scholar PubMed PubMed Central
Stoll, R., Renner, C., Buettner, R., Voelter, W., Bosserhoff, A.K., and Holak, T.A. (2003). Backbone dynamics of the human MIA protein studied by 15N NMR relaxation: implications for extended interactions of SH3 domains. Protein Sci.12, 510–519.10.1110/ps.0222603Search in Google Scholar PubMed PubMed Central
Yu, H., Rosen, M.K., Shin, T.B., Seidel-Dugan, C., Brugge, J.S., and Schreiber, S.L. (1992). Solution structure of the SH3 domain of Src and identification of its ligand-binding site. Science258, 1665–1668.10.1126/science.1280858Search in Google Scholar PubMed
©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal
- Leucine aminopeptidases: diversity in structure and function
- Endogenous anti-inflammatory substances, inter-α-inhibitor and bikunin
- Mitochondrial morphology and distribution in mammalian cells
- Heterogeneity in the cysteine protease inhibitor clitocypin gene family
- Mutations in the inter-SH2 domain of the regulatory subunit of phosphoinositide 3-kinase: effects on catalytic subunit binding and holoenzyme function
- Evaluation of Bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs
- The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine
- Fes1p acts as a nucleotide exchange factor for the ribosome-associated molecular chaperone Ssb1p
- Detailed analysis of MIA protein by mutagenesis
- The role of human tissue kallikreins 7 and 8 in intracranial malignancies
- Prognostic significance of the expression of SR-A1, encoding a novel SR-related CTD-associated factor, in breast cancer
- Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines
- Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells
- Two secreted cystatins of the soft tick Ornithodoros moubata: differential expression pattern and inhibitory specificity
- Acknowledgment
- Contents Biological Chemistry Volume 387, 2006
- Author Index
- Subject Index
Articles in the same Issue
- Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal
- Leucine aminopeptidases: diversity in structure and function
- Endogenous anti-inflammatory substances, inter-α-inhibitor and bikunin
- Mitochondrial morphology and distribution in mammalian cells
- Heterogeneity in the cysteine protease inhibitor clitocypin gene family
- Mutations in the inter-SH2 domain of the regulatory subunit of phosphoinositide 3-kinase: effects on catalytic subunit binding and holoenzyme function
- Evaluation of Bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs
- The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine
- Fes1p acts as a nucleotide exchange factor for the ribosome-associated molecular chaperone Ssb1p
- Detailed analysis of MIA protein by mutagenesis
- The role of human tissue kallikreins 7 and 8 in intracranial malignancies
- Prognostic significance of the expression of SR-A1, encoding a novel SR-related CTD-associated factor, in breast cancer
- Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines
- Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells
- Two secreted cystatins of the soft tick Ornithodoros moubata: differential expression pattern and inhibitory specificity
- Acknowledgment
- Contents Biological Chemistry Volume 387, 2006
- Author Index
- Subject Index
