Receptor tyrosine kinase-GPCR signal complexes

N J Pyne, C Waters, N A Moughal, B S Sambi, S Pyne

Research output: Contribution to journalLiterature review

44 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1220-1225
Number of pages6
JournalBiochemical Society Transactions
Volume31
Issue number6
Publication statusPublished - 1 Dec 2003

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

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