on June 17, 2006
CXCR4 associated proteins and their role in cell specific receptor function
Elena Palmesino and Marcus Thelen
Understanding chemokine receptor-mediated signaling in different cellular environments is the main focus of the project. Ample evidence from our laboratory and by others indicate that coupling of a given G-protein coupled receptor to downstream signaling cascades must be regulated in close proximity to the receptor and may vary between cell types.
As a model we investigate the signaling properties of the chemokine receptor CXCR4 which regulates trafficking of leukocytes and tissue cells and is involved in tumor metastasis. The receptor also mediates cell survival and is important in organogenesis. However, CXCR4-stimulated intracellular signaling depends on the cell system. To characterize receptor-associated proteins, that determine the fate of CXCR4medited cell activation, we developed a solubilization protocol that does not affect the structural integrity of CXCR4, and in which solubilized CXCR4 retains is ability to bind CXCL12. Current investigations should lead to the identification of receptor associated proteins in differ ent cellular systems. Analysis of the expression patterns of the proteins will provide clues on their function in the regulation of CXCR4 activity.