Contribution of receptor/G protein signaling to cell growth and transformation.
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.
Gudermann
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Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany. guderman@mailer.uni-marburg.de
Grosse
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R
Schultz
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G
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011956:Receptors, Cell Surface; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins