The role of the C-terminal tail in protease-activated receptor-2-mediated Ca2+ signalling, proline-rich tyrosine kinase-2 activation, and mitogen-activated protein kinase activity

Michael J Seatter, Robert Drummond, Toru Kanke, Scott R Macfarlane, Morley D Hollenberg, Robin Plevin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

C-terminal truncation mutants were made to investigate the role of the C-terminus in coupling proteinase-activated receptor-2 (PAR-2) to various signalling pathways. Membrane expression of the delta15, delta34, delta43, and delta34-43 mutants was similar; however, expression of deltatail was lost, as was agonist-mediated internalisation of deltatail, delta43, and delta34-43. Additionally, trypsin and SLIGKV-stimulated [3H]IP accumulation was abrogated in cells transiently expressing delta43 or delta34-43 truncations, but remained unaffected in cells expressing delta34 or delta15. PAR-2 agonist-stimulated intracellular Ca(2+) mobilisation and PYK-2 activity were also abolished by deltatail, delta43, and delta34-43 mutants. However, trypsin-stimulated stress-activated protein kinases (SAPKs) or extracellular signal-regulated kinase (ERK) activities were unaffected by the delta34-43 mutation, although activity was abrogated following delta43 or deltatail truncations, suggesting that Ca(2+) mobilisation, PYK-2, or receptor internalisation are not requied for activation of SAPKs or ERK. These studies identify a novel sequence within the PAR-2 C-terminus essential for InsP(3) generation and PYK-2 activity but not mitogen-activated protein kinase (MAPK) activation.

Original languageEnglish
Pages (from-to)21-29
Number of pages9
JournalCellular Signalling
Volume16
Issue number1
Early online date16 Jul 2003
DOIs
Publication statusPublished - Jan 2004

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Keywords

  • amino acid sequence
  • animals
  • COS cells
  • calcium signaling
  • cell membrane
  • cercopithecus aethiops
  • endocytosis
  • focal adhesion kinase 2
  • inositol phosphates
  • MAP kinase signaling system
  • mitogen-activated protein kinase 8
  • mitogen-activated protein kinases
  • mutation
  • protein structure, tertiary
  • protein-tyrosine kinases
  • receptor, PAR-2

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