Bauer, Richard and Humphries, Martin and Fässler, Reinhard and Winklmeier, Andreas and Craig, Sue E and Bosserhoff, Anja-Katrin (2006) Regulation of integrin activity by MIA. The Journal of biological chemistry 281 (17), pp. 11669-11677.
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Other URL: http://dx.doi.org/10.1074/jbc.M511367200
MIA (melanoma inhibitory activity) has been identified as a small protein secreted from malignant melanoma cells, which interacts with extracellular matrix proteins including fibronectin. Here, we show that MIA negatively regulates the activity of the mitogen-activated protein kinase pathway in malignant melanoma. Using far Western blotting and co-immunoprecipitation we searched for MIA-binding cell surface proteins. We found that MIA interacts with integrin alpha4beta1 and alpha5beta1, leading to down-regulation of integrin activity and reduction of mitogen-activated protein kinase signaling. These findings also suggest that MIA may play a role in tumor progression and the spread of malignant melanomas via mediating detachment of cells from extracellular matrix molecules by modulating integrin activity. Inhibiting MIA functions in vivo may therefore provide a novel therapeutic strategy for metastatic melanoma disease.
|Date:||28 April 2006|
|Institutions:|| Medicine > Lehrstuhl für Dermatologie und Venerologie|
Medicine > Lehrstuhl für Pathologie
|Subjects:||500 Science > 570 Life sciences|
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||29 Mar 2007|
|Last Modified:||20 Jul 2011 21:05|