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Crosstalk Among Receptor Signaling Pathways

Haluk Resat, Principal Investigator

Receptor downregulation
The epidermal growth factor receptor (EGFR) system plays an important role in cell proliferation and differentiation. Click for a larger version.

Receptor systems are instrumental for cells to communicate with their surroundings, and receptor signaling pathways control many key biological processes. Although crosstalk between cellular signaling pathways is believed to play a central role in cell biology, receptor transactivation is not well understood. For the Crosstalk Among Receptor Signaling Pathways project, we are partnering with ongoing experimental efforts at Pacific Northwest National Laboratory (PNNL) to investigate how epidermal growth factor receptor (EGFR) signaling is transmodulated by other signaling pathways, such as the insulin-like growth factor-1 receptor (IGF-1R) signaling.

Many aspects of cell receptor signaling are exemplified by the EGFR system. In addition to receptor trafficking and ligand-receptor activity, the EGFR signaling pathway is known to be interconnected to other receptor pathways, including the IGF-1R, insulin receptor (IR), tumor necrosis factor receptor (TNFR), and G-protein coupled receptor (GPCR) pathways. We are using computational approaches to study how different but coupled receptor signaling pathways can transactivate each other. Efforts on this project will result in the development of a signaling pathway for IGF-1R and connecting it to our EGFR model to form a unified signaling network model that includes the crosslinks between different receptor signaling pathways thus allowing us to study the signal transmodulation properties. Our efforts in the Crosstalk Among Receptor Signaling Pathways project also contribute to the aims of the international Receptor Tyrosine Kinase Networks Consortium (RTK) that we participate in as one of the founding members.

Systems Biology at PNNL

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