Trends in Neurosciences
GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences
Section snippets
Transactivation of the EGF receptor by GPCRs
The epidermal growth factor (EGF) receptor ErbB1 is endogenously expressed in numerous cell types, including neurons of the cerebral cortex, cerebellum, hippocampus and other regions of the CNS. It is an important factor in the control of many fundamental biological processes, including the cell cycle, cell migration, metabolism and survival, and cell proliferation and differentiation [22]. The EGF ligand is expressed in several regions of the CNS, where it exerts neurotrophic and
Involvement of the PDGF receptors in dopamine-induced synaptic transmission
Platelet-derived growth factor (PDGF) is one of the most potent RTK mitogens responsible for angiogenesis, cell growth, proliferation, changes in cell shape, motility, migration, and embryonic development. It exerts its cellular effects by binding to and activating structurally related α and β receptors [44]. PDGF acts in both autocrine and paracrine fashions to activate multiple signaling proteins, including PLCγ, PtdIns3-K and MAPKs. Overproduction of PDGF has been implicated in the
Role of the FGF receptor in GPCR-mediated signaling
Fibroblast growth factors (FGFs) are members of a family of polypeptides synthesized by a variety of cell types during embryonic development and in adult tissues. FGF receptors are present in normal and malignant cells, and exert effects on multiple processes, including mitogenesis, angiogenesis, cell differentiation and development. Genetic studies have shown the crucial role of FGFs during early stages of embryogenesis, when embryonic cells depend on FGF signaling for gene expression,
GPCR-induced transactivation of Trk receptors
The neurotrophins NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4) are essential for the development of the CNS. Each neurotrophin can signal through two different types of cell surface receptor: the tropomyosin-related kinase (Trk) RTKs and the p75 neurotrophin receptor (p75NTR), which exhibit independent signaling properties. NGF preferentially binds to trkA, BDNF and NT4 to trkB, and NT3 to trkC. Neurotrophin signaling is an important factor in
Concluding remarks
Recent studies in numerous cell types have established the potential involvement of RTKs in transducing the growth-promoting signals of GPCRs. The recent discovery that RTKs can also regulate GPCR-mediated neuronal transmission has further increased our understanding of the complex interactions between the specific signaling systems in the CNS. Numerous neurotransmitters and neuropeptides that are coupled to GPCRs elicit a wide variety of functions in the CNS, and only a few have been
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