GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences

doi:10.1016/j.tins.2003.11.003

Trends in Neurosciences

Volume 27, Issue 1, January 2004, Pages 48-53

https://doi.org/10.1016/j.tins.2003.11.003 Get rights and content

Abstract

G protein-coupled receptors (GPCRs) mediate cellular responses to a diverse array of extracellular messenger molecules. Recent studies have shown that GPCR-mediated signaling pathways include transactivation of receptor tyrosine kinases (RTKs), such as receptors for epidermal growth factor, platelet-derived growth factor, neurotrophins and fibroblast growth factor. Cross-communication between GPCRs and RTKs is a complex process, and utilizes sets of signaling molecules that are primarily determined by cell context and the types of receptors activated. The differential involvement of RTKs and downstream signaling pathways activated in response to GPCR-mediated stimulation elicits a variety of cellular effects during development, proliferation, differentiation, survival, repair and synaptic transmission in the CNS.

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 (p75^NTR), 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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Published by Elsevier Ltd.

Trends in Neurosciences

GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences

Abstract

Section snippets

Transactivation of the EGF receptor by GPCRs

Involvement of the PDGF receptors in dopamine-induced synaptic transmission

Role of the FGF receptor in GPCR-mediated signaling

GPCR-induced transactivation of Trk receptors

Concluding remarks

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Neuron

Dev. Cell

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Exp. Cell Res.

Prog. Neurobiol.

Int. J. Biochem. Cell Biol.

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Cell

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Neurosci. Lett.

Brain Res.

J. Biol. Chem.

Neuron

Trends Pharmacol. Sci.

Neurosci. Lett.

Neuropharmacology

Eur. J. Pharmacol.

J. Biol. Chem.

Seven-transmembrane receptors

Nat. Rev. Mol. Cell Biol.

Protein kinase C-ε plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 cells

Cell Growth Differ.

MAPK, CREB and zif268 are all required for the consolidation of recognition memory

Philos. Trans. R. Soc. Lond. B Biol. Sci.

The developing synapse: construction and modulation of synaptic structures and circuits

Science

Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory?

J. Neurosci. Res.

Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration

Dev. Neurosci.

PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation

Nat. Neurosci.

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Neurosignals

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Nat. Neurosci.

Activation and targeting of mitogen-activated protein kinases by G-protein-coupled receptors

Can. J. Physiol. Pharmacol.