| dc.description.abstract | Rap1 is a monomeric G protein belonging to the Ras superfamily. As other G proteins, Rap1 cycles between a GTP-bound, active state and a GDP-bound, inactive state. Rap1 was first discovered to inhibit the transforming properties of Ras. Later it was found to have several functions. Depending on the subcellular context, Rap1 can either inhibit the Raf/MEK/ERK pathway by binding Raf-1 in an inactive complex, or activate the Raf/MEK/ERK pathway by activating B-Raf. The subcellular pool of Rap1 at the plasma membrane is responsible for its effects on the Raf/MEK/ERK pathway.
Besides the Raf/MEK/ERK pathway, Rap1 has been found to be involved in integrin activation and adherens junction formation. Rap1 can activate integrins by enhancing its affinity and avidity. Furthermore, Rap1 is responsible for the maturation of adherens junctions by inducing cadherin recruitment to newly forming adherens junctions.
Adherent cells depend on the adherence to the extracellular matrix in order to allow proliferation. This is mediated through integrins. On the other hand, adherens junctions inhibit proliferation in order to inhibit unchecked growth. Thus, extracellular growth signals must ne well coordinated with signals from integrins and cadherins in order for proper proliferation to take place. The scope of this thesis is to determine whether Rap1 could interconnect growth signals activating the Raf/MEK/ERK pathway and integrin activation and/or adherens junction formation, allowing coordination of these separate events. | |
