Extracellular kinases - protein phosphorylation
We have recently discovered that the secreted endogenous Matrix Metalloproteinases (MMPs) and angiogenesis inhibitor Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) is post-translationally modified by the protein tyrosine kinase c-Src in the extracellular space. This phosphorylation appears to regulate the inhibitory activity of TIMP-2 against active MMP-2 and modulate TIMP-2 interaction with the latent proMMP-2 controlling proenzyme processing.
We intend to characterize further the molecular events leading to TIMP-2 phosphorylation and the broader role of secreted c-Src in cell signaling. With this knowledge, we will identify novel signaling networks in cancer and potential new therapeutic targets will emerge to restrict the spread of cancer.
Sánchez-Pozo J, Baker-Williams AJ, Woodford MR, Bullard R, Wei B, Mollapour M, Stetler-Stevenson WG, Bratslavsky G, Bourboulia D. Extracellular Phosphorylation of TIMP-2 by Secreted c-Src Tyrosine Kinase Controls MMP-2 activity. iScience 2018, 1, 87-96. 10.1016/j.isci.2018.02.004
Bourboulia D, and Stetler-Stevenson WG. Matrix MetalloProteinases (MMPs) and Tissue Inhibitors of MetalloProteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 2010, 20, 161-168. PMID: 20470890