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We will demonstrate EGFR phosphorylation and its inhibition in vitro and in cells.

EGF Signal Transduction Pathway

To demonstrate functional relevance, we will prepare a p38 construct that can be switched on by adding a small molecule a chemical dimerizer that translocates the enzyme to the plasma membrane Aim 3. Once successful, we will use similar constructs to translocate proteins that we already identified by an RNAi screen as essential for PIP3-induced endocytosis, e.

As a readout, we will use the fluorescently labeled receptor variants from Aim 2 in live cells. The combined results will help to better understand receptor internalization mechanisms in the absence of a ligand.

Echovirus 1 internalization negatively regulates epidermal growth factor receptor downregulation

Any protein essential for this process must be considered a prime target for novel therapeutics to reduce cell surface growth factor receptor levels and cancer progression. Chemical Biology is moving from a tool delivery field to enabling significant discoveries in biology in the same lab that develops the tool. Therefore more and more synthesis-oriented Chemical Biology labs embrace cell biology and in some cases even physiology and medicine. This proposal is an example where the synthesis of a highly functionalized lipid derivative, as well as the use of non-canonical amino acids and chemical switches will help to identify and characterize new players involved in driving the elimination of growth factor receptors from the cell surface, a crucial step to limit uncontrolled tissue growth, e.

Specifically, identifying key players such as p38 and PAR3 and their mechanism of action will provide new targets for small molecules to interfere with receptor internalization and to treat cancer.

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Internalization of the epidermal growth factor receptor: role in signalling.

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Chemical biology tools for studying growth factor receptor internalization - Carsten Schultz

Recently added grants:. Funding Agency. Name Oregon Health and Science University. The polarized delivery of this transporter between basal and apical cellular regions aids the formation of an auxin morphogenic axis which is crucial in signaling during plant development.

In humans aberrant Wnt signaling has been implicated in many developmental disorders including neurodegenerative diseases and cancer, and so it will be interesting to establish whether a de-regulation of retromer function may be important in these diseases. Our research into this area of sorting nexin biology focuses on two aspects:. Do sorting nexins co-ordinate endosomal sorting of internalised receptors with an ability to modulate receptor signalling?


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Our research into this area of sorting nexin biology focuses on two aspects: defining the role of the RA domain-containing sorting nexin in the endosomal sorting and signaling of Ras small GTPases.