KRAS-Gα ETKİLEŞİMİNİN AŞAĞI AKIŞ YOLLARINI DÜZENLEMEDEKİ ROLÜ

KRAS protein, a member of small G proteins, is responsible for relaying signals in several signaling pathways, including cell survival, growth and proliferation. Traditionally, biological implication of KRAS has been considered via a canonical mechanism where it functions as a molecular switch that cycles between on and off state through GDP/GTP binding. Though the GTPase cycle remains crucial, it does not fully explain how complex and specific KRAS signaling is in different cellular environments. Oncogenic KRAS signaling modulation continues as the crucial field in understanding cancer biology. Prior FRET results in our group showed a noncanonical physical interaction between KRAS and distinct Gα subunits that are able to produce stable heterodimers. It suggests that neither KRAS nor Gα proteins function individually but they possibly connect two crucial signaling families. Following this previous structural evidence, this study aims to shed light on functional significance of these KRAS-Gα heterodimers, not only assessing if these heterodimers trigger signaling but also how they specifically modulate, suppress or bias crucial signaling mechanisms where they individually have a role, including MAPK/ERK, PI3K/AKT and RHO/ROCK pathways.