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Endothelins stimulate tyrosine phosphorylation and activity of p42/mitogen-activated protein-kinase in astrocytes

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Overview

authors

  • Cazaubon, S.
  • Parker, P. J.
  • Strosberg, Donny
  • Couraud, P. O.

publication date

  • July 1993

journal

  • Biochemical Journal  Journal

abstract

  • Endothelins (ET-1, -2, -3) display pleiotropic activities, by signalling through G-protein-coupled membrane receptors. We show here that ET-1 and ET-3 stimulate within minutes the tyrosine phosphorylation of a 42 kDa protein (p42) in primary cultures of mouse embryo astrocytes, but not in any of two subclones of rat astrocytoma C6 cells. This effect, measured by anti-phosphotyrosine immunoblotting of cell extracts, was also observed in response to bradykinin, platelet-derived growth factor, the phorbol ester phorbol 12-myristate 13-acetate and the G-protein activator fluoroaluminate. Pretreatment of cells with pertussis toxin, which inactivates Gi/G(o) proteins, did not affect these responses. However, down-regulation of protein kinase C completely blocked the response to phorbol ester and fluoroaluminate and at least partially impaired the ET-1-stimulated phosphorylation of p42. We have identified p42 as p42mapk, a mitogen-activated protein (MAP) kinase, on the basis of the following data: by sequential immunoblotting with antiphosphotyrosine and anti-MAP kinase antibodies, (i) similar kinetics are observed for p42 phosphorylation and the decrease in p42mapk electrophoretic mobility, likely corresponding to its tyrosine/threonine phosphorylation [de Vries-Smits, Boudewijn, Burgering, Leevers, Marshall and Bos (1992) Nature (London) 357, 602-604]; (ii) p42 and the shifted form of p42mapk co-migrate on SDS/PAGE; (iii) the myelin-basic-protein kinase activity of p42mapk is stimulated by ET-1, in parallel with the tyrosine phosphorylation of p42. In conclusion, these findings strongly suggest that endothelins can stimulate the tyrosine phosphorylation and activation of p42mapk in astrocytes, via pertussis-toxin-insensitive G protein and protein kinase C-dependent and -independent pathways.

subject areas

  • Aluminum
  • Aluminum Compounds
  • Animals
  • Astrocytes
  • Astrocytoma
  • Clone Cells
  • Endothelins
  • Enzyme Activation
  • Fluorides
  • Glycogen Synthase Kinase 3
  • Ligands
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Phosphorylation
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Rats
  • Tetradecanoylphorbol Acetate
  • Tumor Cells, Cultured
  • Tyrosine
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Identity

PubMed Central ID

  • PMC1134371

International Standard Serial Number (ISSN)

  • 0264-6021

PubMed ID

  • 8343118
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Additional Document Info

start page

  • 381

end page

  • 386

volume

  • 293

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