| Project Overview: | Signalling through the epidermal growth factor receptor (EGFR) is initiated by the release of mature ligands from their membrane-anchored precursor forms, a process referred to as ‘‘ectodomain shedding’’. This proteolytic event is executed by a disintegrin and metalloproteases (ADAMs) and often triggered by the activation of protein kinase C (PKC), yet the underlying mechanisms are poorly understood. The objective of the project is to identify novel factors regulating ADAM-mediated ectodomain shedding downstream of PKC by performing siRNA library screening. No siRNA screens have been reported on the regulation of ADAM protease activity. With the proposed research, we expect to identify novel PKC-dependent regulators of ADAM protease activity, thereby gaining important insight into the mechanism of growth factor signalling. ADAMs are intensively studied as potential drug targets and identifying regulators of ADAM protease activity may allow more precise protease intervention by preventing interaction with these regulators – an exciting alternative to traditional protease inhibition that may afford a distinct pattern of specificity. |
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| Screener: | Marie Kveiborg (Parker Lab). Extension:3505, Rm 203 |
| Project Status: | Published |
| Publications: | The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17.. Dombernowsky et al., 2015 |
| Project Start Date: | Mar 2009 |
| Keywords: | ADAM proteases HT1080 PKC |
| Libraries Screened: |
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