Receptor tyrosine kinase–GPCR signal complexes. (1st December 2003)

• Record Type: Journal Article
• Authors: Pyne, N.J.; Waters, C.; Moughal, N.A.; Sambi, B.S.; Pyne, S.
• Is Part Of: Biochemical Society transactions. Volume 31:Number 6(2003)
• Page Start: 1220
• Page End: 1225
• Publication Date: 2003-12-01
• Subjects: differentiation -- growth factor receptor -- lysophosphatidic acid -- p42/p44 mitogen-activated protein kinase -- proliferation -- sphingosine 1-phosphate (S1P); Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0311220
• Languages: English
• ISSNs: 0300-5127

Abstract

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 Gi α, 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.