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Contribution of receptor/G protein signaling to cell growth and transformation
T Gudermann1, R Grosse, G Schultz
1Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany. guderman@mailer.uni-marburg.de
Abstract:
While the effects of receptor/G protein systems on intermediary metabolism have been intensively studied, it has only recently been appreciated that G protein-coupled receptors and G proteins (heterotrimeric GTP-binding proteins) play important roles in the regulation of cell growth, differentiation and even transformation. Naturally occurring mutations both in G protein-coupled receptors and in G protein alpha-subunits lead to autonomous cell growth resulting in human disease. One mechanism to transduce mitogenic signals from the cell membrane to the nucleus is the engagement of the extracellular signal-regulated kinase (ERK)mitogen-activated protein kinase (MAPK) cascade. Multiple distinct signal transduction pathways have been characterized which link G proteins with the ERK cascade. Receptor and non-receptor tyrosine kinases play central roles in these pathways. Mitogenic signaling by receptor/G protein systems is realized as a complex interplay between signals emanating from different classes of cell surface receptors. The characterization of receptor-, G protein- and tyrosine kinase-specific contributions to mitogenic signaling in a particular cell may ultimately allow for the rational design and application of pharmaceuticals to treat diseases involving uncontrolled cell proliferation.
Insights
G protein-coupled receptors and G proteins regulate cell growth and differentiation. Understanding these pathways, including the ERK-MAPK cascade, can lead to new treatments for diseases involving uncontrolled cell proliferation.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- G protein-coupled receptors (GPCRs) and G proteins are increasingly recognized for their roles in cell growth, differentiation, and transformation.
- Mutations in GPCRs and G protein alpha-subunits can cause autonomous cell growth and human diseases.
- The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) cascade is a key pathway for transducing mitogenic signals.
Purpose of the Study:
- To elucidate the mechanisms by which G protein-coupled receptors and G proteins regulate cell growth.
- To characterize the signaling pathways linking G proteins to the ERK-MAPK cascade.
- To explore the potential for therapeutic interventions targeting these pathways.
Main Methods:
- Review of existing literature on G protein signaling and cell proliferation.
- Analysis of signal transduction pathways involving GPCRs, G proteins, and tyrosine kinases.
- Discussion of the interplay between different cell surface receptor systems.
Main Results:
- Multiple signaling pathways connect G proteins to the ERK cascade.
- Receptor and non-receptor tyrosine kinases are central to these mitogenic signaling pathways.
- G protein-coupled receptor and G protein systems are integral to complex cell surface receptor signaling networks.
Conclusions:
- Characterizing receptor, G protein, and tyrosine kinase contributions to mitogenic signaling is crucial.
- This understanding may enable the rational design of pharmaceuticals for diseases with uncontrolled cell proliferation.
- Targeting these pathways offers potential therapeutic strategies for proliferative disorders.