The formation of complexes between growth factor receptors and members of a family of G-protein-coupled receptors whose natural ligands are S1P (sphingosine 1-phosphate) and LPA (lysophosphatidic acid) represents a new signalling entity. This receptor complex allows for integrated signalling in response to growth factor and/or S1P/LPA and provides a mechanism for more efficient activation (due to integrated close-proximity signalling from both receptor classes) of the p42/p44 MAPK (mitogen-activated protein kinase) pathway. This article provides information on the molecular events at the interface between receptor tyrosine kinases and S1P/LPA receptors. Examples include the PDGF (platelet-derived growth factor)-induced tyrosine phosphorylation of Giα, released upon S1P1 receptor activation, which is required for initiation of the p42/p44 MAPK pathway. Critical to this event is the formation of endocytic vesicles containing functionally active PDGFβ receptor–S1P1 receptor complexes, which are internalized and relocated with components of the p42/p44 MAPK pathway. We also report examples of cross-talk signal integration between the Trk A (tropomyosin receptor kinase A) receptor and the LPA1 receptor in terms of the NGF (nerve growth factor)-dependent regulation of the p42/p44 MAPK pathway. NGF induces recruitment of the LPA1 receptor to the nucleus (delivery might be Trk A-dependent), whereupon the LPA1 receptor may govern gene expression via novel nuclear signalling processes.
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Conference Article| December 01 2003
Receptor tyrosine kinase–GPCR signal complexes
N.J. Pyne 1
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor St, Glasgow G4 0NR, U.K.
1To whom correspondence should be addressed (e-mail firstname.lastname@example.org).
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Biochem Soc Trans (2003) 31 (6): 1220–1225.
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N.J. Pyne, C. Waters, N.A. Moughal, B.S. Sambi, S. Pyne; Receptor tyrosine kinase–GPCR signal complexes. Biochem Soc Trans 1 December 2003; 31 (6): 1220–1225. doi: https://doi.org/10.1042/bst0311220
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