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Mechanisms of Regulated Ligand Shedding

Brian Thrall, Principal Investigator

Regulated proteolytic release of membrane-bound proteins, called ectodomain shedding, is a central mechanism by which cells communicate information and respond to environmental changes. As part of the Mechanisms of Regulated Ligand Shedding project at Pacific Northwest National Laboratory (PNNL), technologies and a knowledge base are being developed that will allow us to understand temporal and spatial regulation of ectodomain shedding. The many tools and capabilities being used for this study include:

  • microarrays to characterize the cellular expression patterns of metalloproteases and substrates and to determine if their expression is regulated during shedding
  • engineered cells that express chimeric shed ligands combined with microarray immunoassays to discover how enzyme and co-regulator patterns dictate cell-specific and stimulus-specific shedding
  • cell imaging to determine the role of substrate and enzyme compartmentalization in regulated shedding.

By developing the tools necessary to examine global regulation of shedding, new paradigms regarding this process as an integrating signaling system will be revealed. The technical expertise made available through successful execution of this project will be directly applicable to a range of biological problems central to many core missions of the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH).

Systems Biology at PNNL

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