Receptor tyrosine kinase-GPCR signal complexes

Pyne, N J and Waters, C and Moughal, N A and Sambi, B S and Pyne, S (2003) Receptor tyrosine kinase-GPCR signal complexes. Biochemical Society Transactions, 31 (6). pp. 1220-1225. ISSN 0300-5127

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Abstract

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 G(i)alpha, released upon S1P(1) 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 PDGFbeta receptor-S1P(1) 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 LPA(1) receptor in terms of the NGF (nerve growth factor)-dependent regulation of the p42/p44 MAPK pathway. NGF induces recruitment of the LPA(1) receptor to the nucleus (delivery might be Trk A-dependent), whereupon the LPA(1) receptor may govern gene expression via novel nuclear signalling processes.

Creators(s): Pyne, N J ORCID logoORCID: https://orcid.org/0000-0002-5657-4578, Waters, C, Moughal, N A, Sambi, B S and Pyne, S ORCID logoORCID: https://orcid.org/0000-0002-6608-9584;
Item type:Article
ID code:34959
Keywords:cell line, GTP-binding proteins, humans, nerve growth factor, proto-oncogene proteins c-sis, receptor protein-tyrosine Kinases, receptors, cell surface, receptors, G-protein-coupled, receptors, lysophospholipid, signal transduction, Pharmacy and materia medica, Biochemistry
Subjects:Medicine > Pharmacy and materia medica
Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user: Pure Administrator
Date deposited:15 Nov 2011 15:01
Last modified:26 Mar 2020 02:05
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URI:https://strathprints.strath.ac.uk/id/eprint/34959
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