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FRIBIO-Biologi og biomedisin

The study of translocation of extragenous growth factors into cells- mechanisms and biological function of intracellular growth factors.

Tildelt: kr 3,1 mill.

Prosjektleder:

Prosjektnummer:

170482

Søknadstype:

Prosjektperiode:

2006 - 2011

Midlene er mottatt fra:

Geografi:

The growth, development and repair of cells and organs are controlled by a variety of hormones, growth factors and cytokines. Many of these factors are proteins that bind to specific molecules (receptors) at the cell surface. These receptors reside in the plasma membrane. Lipid membranes control the intracellular environment by restricting the transport of molecules in and out of the cell. Small molecules like water and ions can be transported across the membrane in specific channels, while the transport of larger molecules is strictly controlled and less common. Instead of crossing the plasma membrane, signalling molecules can get their message across by binding to the receptors on the outside of the cell. This binding introduces changes in the receptor on the inside of the membrane, and intracellular proteins can sense the signal from the outside. The signalling molecule itself remains bound to the receptors extracellular part, while the signal is being translated into a complicated language where the w ords consist of many chemical components. The study of cell signalling is one of the prime targets in international cancer research, since many forms of cancer is due to failure in this intracellular communication. In our work, we have discovered an alter native route in which information is being transferred to the cell interior. We have observed that a growth factor (FGF1) itself is being transferred into the cell by crossing the plasma membrane. After being translocated into the cytoplasm, FGF1 is rapid ly shuttled to the cell nucleus where it stimulates the synthesis of DNA. After finishing its tasks in the nucleus, FGF1 is shuttled back into the cytoplasm where it is degraded. Our data suggests that the growth factor FGF1 works in a dual mode. Firstly, it binds its receptor on the cell surface and stimulates the receptor activity. Secondly, FGF1 translocates across the cell membrane and is found in both the cytoplasm and in the nucleus of the cell.

Budsjettformål:

FRIBIO-Biologi og biomedisin

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