Receptor tyrosine kinase-GPCR signal complexes

Biochem Soc Trans. 2003 Dec;31(Pt 6):1220-5. doi: 10.1042/bst0311220.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Line
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Nerve Growth Factor / metabolism
  • Proto-Oncogene Proteins c-sis / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Lysophospholipid
  • Signal Transduction*

Substances

  • Proto-Oncogene Proteins c-sis
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Nerve Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • GTP-Binding Proteins