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Transactivation of Receptor Tyrosine Kinases by Dopamine Receptors

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Book cover Dopamine Receptor Technologies

Part of the book series: Neuromethods ((NM,volume 96))

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Abstract

As our understanding of G protein-coupled receptor (GPCR) signaling grows, it is clear that the arsenal of GPCR effectors is far greater than their classical second messenger signaling pathways. The transactivation, or GPCR-induced activation of receptor tyrosine kinases (RTKs), presents an avenue for GPCRs to affect signaling pathways that have previously been attributed to growth factors and opens the door for modulation of RTK activity with small-molecule GPCR ligands. Several RTK transactivation pathways initiated by dopamine receptors have been described. One of the best characterized is the D2-class dopamine receptor transactivation of the platelet-derived growth factor (PDGF) receptor: a ligand-independent, intracellular signaling pathway. Dopamine receptors can also transactivate epidermal growth factor (EGF) receptors, often via the metalloproteinase-dependent cleavage of EGF itself from the cell surface. Although the discovery of RTK transactivation is relatively recent, a growing body of research has identified these pathways in several cell line, primary cell, and in vivo systems. These studies have characterized the time course and magnitude of RTK transactivation and have identified several common effectors involved. The choice of the primary readout in transactivation studies, i.e., RTK activation/phosphorylation or a downstream RTK effector such as extracellular signal-regulated kinases (ERK) or Akt, is an important consideration for transactivation studies. Equally important is identifying whether the transactivation is ligand (growth factor) dependent or independent. These and other considerations are described, not only with a focus on dopamine receptor-initiated transactivation pathways but also with a discussion of general considerations for the study of GPCR–RTK transactivation.

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Correspondence to Michael A. Beazely B.S.P., Ph.D. .

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Kruk, J.S., Kouchmeshky, A., Grimberg, N., Rezkella, M., Beazely, M.A. (2015). Transactivation of Receptor Tyrosine Kinases by Dopamine Receptors. In: Tiberi, M. (eds) Dopamine Receptor Technologies. Neuromethods, vol 96. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2196-6_12

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