Mass spectrometry identification of membrane-type 1 matrix metalloproteinase (MT1-MMP) binding partners following co-immunoprecipitation in MCF-7 cells
Abstract
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an integral multidomain membrane protease involved in extracellular matrix remodelling. No longer recognized solely as a destructive enzyme, MT1-MMP proteolytic and non-proteolytic activities are involved in a variety of cellular processes. I hypothesized that the diverse functions of MT1-MMP are dependent on domain-specific binding partner interactions that elicit a cellular response. Using a combination of co-immunoprecipitation and mass spectrometry, 248 unique proteins were isolated in MT1-MMP variant expressing MCF-7 cells. Newly identified binding partners suggest potential roles of MT1-MMP in the nucleus, endoplasmic reticulum, cytoplasm, and plasma membrane. Additionally, the cytoplasmic domain of MT1-MMP attenuates canonical transforming growth factor beta (TGF-β) signalling through an unknown mechanism. The results of this proteomic study add proteins to a growing catalogue of binding partners involved in proper localization and function of MT1-MMP.