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G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformation
1Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Abstract:
Extracellular signals when routed through signaling pathways that use heterotrimeric G proteins can engage multiple signaling pathways leading to diverse biological consequences. One locus at which signal sorting occurs is at the level of G proteins. G protein alpha-subunits appear to be capable of interacting with different effectors leading to engagement of distinct signaling pathways. Regulation of different pathways in turn leads to different biological outcomes. The process of neoplastic transformation is controlled to a large extent through the activation and inhibition of signaling pathways. Signaling pathways such as the Ras-MAPK, v-Src-Stat3 pathways are activated in the process of transformation. Expression of activated Galpha subunits have been shown to cause transformation of cells. While activation of the MAPK 1,2 pathway by various Galpha subunits has been reported for several years, recent studies show the activation and involvement of Src and Stat3 pathways in Galphao and Galphai mediated transformation of cells. Recent studies also suggest that both Galphai and Galphas may be able to interact with and activate Src. The activation of Src and Stat3 by G proteins has also been demonstrated by ligand-induced activation of G protein receptors. So increasingly it is becoming clear that the Src and Stat3 pathways are potential effectors for G proteins and that they may play a role in G protein function.
Insights
G proteins regulate cell signaling pathways, including Src and Stat3, which are crucial for cell transformation. Understanding these G protein-mediated pathways offers insights into neoplastic transformation and potential therapeutic targets.
Area of Science:
- Cellular Biology
- Molecular Biology
- Oncology
Background:
- Heterotrimeric G proteins mediate extracellular signals, influencing diverse biological outcomes.
- Signal sorting at the G protein level dictates pathway engagement and cellular responses.
- Neoplastic transformation involves dysregulated signaling pathways like Ras-MAPK and v-Src-Stat3.
Purpose of the Study:
- To investigate the role of G protein alpha-subunits in mediating cell transformation.
- To explore the involvement of Src and Stat3 signaling pathways in G protein-mediated transformation.
- To elucidate the mechanisms by which G proteins activate Src and Stat3 pathways.
Main Methods:
- Analysis of G protein alpha-subunit interactions with effectors.
- Investigating the activation of MAPK, Src, and Stat3 pathways by G proteins.
- Studying ligand-induced activation of G protein-coupled receptors and downstream signaling.
Main Results:
- Activated Galpha subunits can induce cellular transformation.
- Src and Stat3 pathways are activated in Galphao and Galphai-mediated transformation.
- Both Galphai and Galphas can interact with and activate Src.
- Ligand-induced G protein receptor activation demonstrates Src and Stat3 activation by G proteins.
Conclusions:
- Src and Stat3 pathways are identified as potential effectors for G proteins.
- G proteins play a significant role in regulating Src and Stat3 signaling.
- These findings highlight the importance of G protein-Src-Stat3 interactions in cell transformation and function.