scholarly journals Dopamine activates ERKs in alveolar epithelial cells via Ras-PKC-dependent and Grb2/Sos-independent mechanisms

2002 ◽  
Vol 282 (5) ◽  
pp. L1099-L1107 ◽  
Author(s):  
Carmen Guerrero ◽  
Liuska Pesce ◽  
Emilia Lecuona ◽  
Karen M. Ridge ◽  
Jacob I. Sznajder
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Present Report ◽  
Classical Model ◽  
Alveolar Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Alveolar Epithelial ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Erk Proteins

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 PKCε. 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.

scholarly journals The Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Induces the Inflammatory Factor Interleukin-8 following Chlamydia trachomatis Infection

2007 ◽  
Vol 75 (12) ◽  
pp. 5924-5929 ◽  
Author(s):  
Kerry R. Buchholz ◽  
Richard S. Stephens
Keyword(s):  
Protein Kinase ◽  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Interleukin 8 ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Diseases associated with Chlamydia infection, such as pelvic inflammatory disease and ectopic pregnancy, are due to inflammation-mediated tissue damage and scarring that occur after chronic or repeated infections. The inflammatory chemokine interleukin-8 (IL-8) is produced by Chlamydia-infected cells through an endogenous mechanism of activation, independent of soluble factors in the supernatant. The host signaling pathways necessary for this response are not understood, but the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) has been shown to be activated at similar times as IL-8 mRNA up-regulation. The purpose of this study was to elucidate the MAPK pathways necessary to induce the endogenous IL-8 response to Chlamydia trachomatis infection of epithelial cells. IL-8 induced by infection with C. trachomatis L2 was shown to be dependent on ERK and independent of p38 and Jun N-terminal MAPK by use of chemical inhibitors of the signaling pathways. Persistent ERK activation during IL-8 mRNA production at 24 h postinfection was necessary to maintain the response. C. trachomatis serovar D also induced IL-8 in an ERK-dependent manner. We concluded that IL-8 induced during infection of epithelial cells is dependent on continual activation of ERK by C. trachomatis.

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