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Projekt 4. - Institut for Matematik og Datalogi - Syddansk Universitet

Projekt 4. - Institut for Matematik og Datalogi - Syddansk Universitet

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N a t u r v i d e n s k a b e l i g t P r o j e k t / F a r m a c e u t : V a l g f r i t P r o j e k t<br />

<strong>Projekt</strong> 29. Importance of protein tyrosine<br />

phosphorylation <strong>for</strong> normal and cancer cell signaling.<br />

Vejleder: Blagoy Blagoev, bab@bmb.sdu.dk<br />

<strong>Institut</strong>: <strong>Institut</strong> <strong>for</strong> Biokemi <strong>og</strong> Molekylær Biol<strong>og</strong>i (BMB)<br />

Praktisk del: CEBI<br />

Gruppeplacering: Biblioteket<br />

Gruppestørrelse: Mindst 3 <strong>og</strong> max 4 deltagere. Én gruppe kan arbejde med projektet.<br />

Kommentarer: The project will be held in English, including the report and examination<br />

Keywords:<br />

signaling, phosphorylation, cancer, kinases, phosphatases, inhibitors<br />

Abstract<br />

In multicellular organisms the proper function and survival of every cell is dependent on intercellular<br />

signalling networks that control cells‟ growth, differentiation and metabolism. Deregulation<br />

of signaling, e.g. loss of growth control, is at the heart of numerous human diseases including<br />

cancer. Growth factors like the epidermal growth factor (EGF), nerve growth factor (NGF) and<br />

Insulin among others play a central role in these processes. The most distinguishing feature of<br />

the cellular signaling initiated by growth factors is the flow of tyrosine phosphorylation events<br />

occurring in the cells immediately after hormone stimulation. Improper actions of the proteins<br />

responsible <strong>for</strong> the reversible tyrosine phosphorylation, namely tyrosine kinases and phosphatases,<br />

are found in all human cancers and are the main cause <strong>for</strong> developing and maintaining the<br />

disease state. There<strong>for</strong>e, the development of specific inhibitors to various kinases and phosphatases<br />

take a central part of the drug-developing industry today.<br />

Plan <strong>for</strong> experimental work: In this project we will study protein tyrosine phosphorylation induced<br />

by growth factors in cancer cell lines using immunoprecipitation and Western blotting.<br />

This experiment will be repeated using specific inhibitors of tyrosine phosphatases in order to<br />

compare the cellular effects under these experimental conditions. The project will reveal both the<br />

global cellular phosphorylation responses as well as some of the key proteins involved in the<br />

signaling initiated by growth factors. The project provides an opportunity to work with cell culture<br />

and some of the major molecular biol<strong>og</strong>y techniques.<br />

Minikurser<br />

Obligatorisk: <strong>Projekt</strong>arbejde (Microsoft, Nat)<br />

Anbefalede: Ingen<br />

Litteraturliste over metode artikler, som udleveres til de studerende<br />

Blume-Jensen P, Hunter T. Onc<strong>og</strong>enic kinase signalling. Nature. 2001, 411(6835):355-65.<br />

Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2000, 103(2):211-25.<br />

Hunter T. Signaling--2000 and beyond. Cell. 2000, 100(1):113-27.<br />

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