Receptor tyrosine kinase-G-protein-coupled receptor signalling platforms: out of the shadow?

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Abstract

Receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs) can form platforms in which protein signalling components specific for each receptor are shared (owing to close proximity) to produce an integrated response upon engagement of ligands. RTK-GPCR signalling platforms respond to growth factors and GPCR agonists to increase gain over and above that which is normally produced by separate receptors. They can also function to change the spatial context of signalling in response to growth factor activation. The function of RTK-GPCR signalling platforms can be modulated with conformational-specific inhibitors that stabilise defined GPCR states to abrogate both GPCR agonist- and growth factor-stimulated cell responses. In this paper, we provide an opinion of the biology and unusual pharmacology of RTK-GPCR signalling platforms and make comparisons with a more traditional model of crosstalk between RTKs and GPCRs.
LanguageEnglish
Pages443-450
Number of pages8
JournalTrends in Pharmacological Sciences
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 2011

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G-Protein-Coupled Receptor Kinases
Receptor Protein-Tyrosine Kinases
G-Protein-Coupled Receptors
Intercellular Signaling Peptides and Proteins
Crosstalk
Chemical activation
Ligands
Pharmacology
Proteins

Keywords

  • ligands
  • signalling platforms
  • receptors
  • cell responses

Cite this

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title = "Receptor tyrosine kinase-G-protein-coupled receptor signalling platforms: out of the shadow?",
abstract = "Receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs) can form platforms in which protein signalling components specific for each receptor are shared (owing to close proximity) to produce an integrated response upon engagement of ligands. RTK-GPCR signalling platforms respond to growth factors and GPCR agonists to increase gain over and above that which is normally produced by separate receptors. They can also function to change the spatial context of signalling in response to growth factor activation. The function of RTK-GPCR signalling platforms can be modulated with conformational-specific inhibitors that stabilise defined GPCR states to abrogate both GPCR agonist- and growth factor-stimulated cell responses. In this paper, we provide an opinion of the biology and unusual pharmacology of RTK-GPCR signalling platforms and make comparisons with a more traditional model of crosstalk between RTKs and GPCRs.",
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author = "Pyne, {Nigel J} and Susan Pyne",
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AU - Pyne, Susan

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AB - Receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs) can form platforms in which protein signalling components specific for each receptor are shared (owing to close proximity) to produce an integrated response upon engagement of ligands. RTK-GPCR signalling platforms respond to growth factors and GPCR agonists to increase gain over and above that which is normally produced by separate receptors. They can also function to change the spatial context of signalling in response to growth factor activation. The function of RTK-GPCR signalling platforms can be modulated with conformational-specific inhibitors that stabilise defined GPCR states to abrogate both GPCR agonist- and growth factor-stimulated cell responses. In this paper, we provide an opinion of the biology and unusual pharmacology of RTK-GPCR signalling platforms and make comparisons with a more traditional model of crosstalk between RTKs and GPCRs.

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KW - receptors

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