| Title |
Nck adaptorinio baltymo ir p120 Ras GTPazę aktyvinančio baltymo sąveikos mechanizmas bei vaidmuo Ras aktyvumo reguliavime / |
| Translation of Title |
The mechanism and the role of adaptor protein Nck interaction with p120 Ras GTPase-activating protein in Ras regulation. |
| Authors |
Ger, Marija |
| Full Text |
|
| Pages |
116 |
| Keywords [eng] |
proliferation ; Ras ; protein-protein interactions |
| Abstract [eng] |
This study was focused on complex between the adaptor protein Nck1 and p120 RasGTPase-activating protein and its role in the cell. The family of small G-proteins Ras are crucial intracellular regulators of growth factor signaling. The main negative regulator of Ras is p120 RasGAP. We have discovered that adaptor proteins Nck1 and Nck2 associate with p120 RasGAP. This interaction does not change upon the short-term stimulation with platelet-derived growth factor BB (PDGF-BB) and is present in various cell lines. By means of confocal microscopy we have shown that Nck1 and p120 RasGAP colocalize in the cell. Using various Nck1 mutants we have elucidated that SH3-I and SH3-III domains of Nck1 associate with N-terminal proline-rich sequence of RasGAP. Nck1 associate with p120 RasGAP directly in vitro. The complex between adaptor protein Nck and RasGAP dissociates after the adherent cell detachment due to unidentified conformational change of p120 RasGAP. Nck1 association with p120 RasGAP increases RasGAP catalytic activity, and overexpression of Nck1 decreases p120 RasGAP-regulated PDGF-BB-induced Ras activation. Accordingly, the dissociation of complex between Nck1 and p120 RasGAP after the cell detachment corellates with the increase in Ras activity. The data reveals a new role of Nck1 adaptor protein as the modulator of Ras activity. |
| Type |
Doctoral thesis |
| Language |
Lithuanian |
| Publication date |
2009 |
