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

43 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.
LanguageEnglish
Pages1220-1225
Number of pages6
JournalBiochemical Society Transactions
Volume31
Issue number6
Publication statusPublished - 1 Dec 2003

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Lysophosphatidic Acid Receptors
Mitogen-Activated Protein Kinase 1
Receptor Protein-Tyrosine Kinases
Mitogen-Activated Protein Kinases
Lysosphingolipid Receptors
Nerve Growth Factor
Chemical activation
Transport Vesicles
Tropomyosin
Phosphorylation
Growth Factor Receptors
Platelet-Derived Growth Factor
G-Protein-Coupled Receptors
Gene expression
Tyrosine
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Ligands
Gene Expression
sphingosine 1-phosphate

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

Cite this

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.
Pyne, N J ; Waters, C ; Moughal, N A ; Sambi, B S ; Pyne, S. / Receptor tyrosine kinase-GPCR signal complexes. In: Biochemical Society Transactions. 2003 ; Vol. 31, No. 6. pp. 1220-1225.
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Pyne, NJ, Waters, C, Moughal, NA, Sambi, BS & Pyne, S 2003, 'Receptor tyrosine kinase-GPCR signal complexes' Biochemical Society Transactions, vol. 31, no. 6, pp. 1220-1225.

Receptor tyrosine kinase-GPCR signal complexes. / Pyne, N J; Waters, C; Moughal, N A; Sambi, B S; Pyne, S.

In: Biochemical Society Transactions, Vol. 31, No. 6, 01.12.2003, p. 1220-1225.

Research output: Contribution to journalLiterature review

TY - JOUR

T1 - Receptor tyrosine kinase-GPCR signal complexes

AU - Pyne, N J

AU - Waters, C

AU - Moughal, N A

AU - Sambi, B S

AU - Pyne, S

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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.

AB - 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.

KW - cell line

KW - GTP-binding proteins

KW - humans

KW - nerve growth factor

KW - proto-oncogene proteins c-sis

KW - receptor protein-tyrosine Kinases

KW - receptors, cell surface

KW - receptors, G-protein-coupled

KW - receptors, lysophospholipid

KW - signal transduction

UR - http://www.biochemsoctrans.org/bst/031/bst0311220.htm

M3 - Literature review

VL - 31

SP - 1220

EP - 1225

JO - Biochemical Society Transactions

T2 - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 0300-5127

IS - 6

ER -

Pyne NJ, Waters C, Moughal NA, Sambi BS, Pyne S. Receptor tyrosine kinase-GPCR signal complexes. Biochemical Society Transactions. 2003 Dec 1;31(6):1220-1225.