Extracellular kinases - protein phosphorylation
Innovative work in the field of extracellular chaperones from the Bourboulia Lab has resulted in the identification of TIMP2 (Bourboulia & Stetler-Stevenson, Semin Can Biol 2010), an endogenous inhibitor of angiogenesis and matrix proteolysis, as (a) the first secretory co-chaperone of extracellular molecular chaperone HSP90 (eHSP90) (Baker-Williams et al., Cell Rep 2019; Votra et al., MIMB, 2023) and (b) a phosphoprotein and extracellular substrate of secreted tyrosine kinase c-Src (Sánchez-Pozo et al., iScience 2018; Truman et al., JBC 2021). Bourboulia’s recent work has demonstrated a new paradigm for Src regulation of the extracellular milieu, particular for disease states where c-Src is hyperactive (Backe et al., Cell Rep 2023; Omini et al., STAR Prot 2023).
BourbouliaLab
Relevant Publications
Backe SJ, Votra SD, Stokes MP, Sebestyén E, Castelli M, Torielli L, Colombo G, Woodford MR, Mollapour M, Bourboulia D. PhosY-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.
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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
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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