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1 Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611; and 2 Centro de Investigación del Cáncer, Universidad de Salamanca, 37007 Salamanca, Spain
Recently it has
been described that dopamine (DA), via dopaminergic type 2 receptors
(D2R), activates the mitogen-activated protein kinase
extracellular signal-regulated kinase (MAPK/ERK) proteins in alveolar
epithelial cells (AEC), which results in the upregulation of
Na+-K+-ATPase. In the present report, we used
AEC to investigate the signaling pathway that links DA with ERK
activation. Incubation of AEC with DA resulted in rapid and transient
stimulation of ERK activity, which was mediated by Ras proteins and the
serine/threonine kinase Raf-1. Pretreatment of AEC with Src
homology 3 binding peptide, which blocks the interaction between Grb2
and Sos, did not prevent DA activation of ERK. Diacylglycerol
(DAG)-dependent protein kinase C (PKC) isoenzymes, involved in the
DA-mediated activation of ERK proteins as pretreatment with
either bisindolylmaleimide or Ro-31-8220, prevented the
phosphorylation of Elk-1, and quinpirole, a D2R activator,
stimulates the translocation of PKC
. Together, the data
suggest that DA activated MAPK/ERK via Ras, Raf-1 kinase, and
DAG-dependent PKC isoenzymes, but, importantly and contrary to the
classical model, this pathway did not involve the Grb2-Sos complex formation.
alveolar epithelial cell; mitogen-activated protein kinase/extracellular signal-regulated kinase; protein kinase C
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