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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.


Relevant Publications


Backe SJ, Votra SD, Stokes MP, Sebestyén E, Castelli M, Torielli L, Colombo G, Woodford MR, Mollapour M, Bourboulia DPhosY-secretome profiling combined with kinase-substrate interaction screening defines active c-Src-driven extracellular signaling. Cell Rep. 2023 Jun 27;42(6):112539. doi: 10.1016/j.celrep.2023.112539. Epub 2023 May 25. PubMed PMID: 37243593; NIHMSID:NIHMS1912762.

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

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