Stimulation of α1A-Adrenoceptors in Rat-1 Cells Inhibits Extracellular Signal-Regulated Kinase by Activating p38 Mitogen-Activated Protein Kinase

1998 ◽  
Vol 54 (5) ◽  
pp. 755-760 ◽  
Author(s):  
Alexander Alexandrov ◽  
Susanne Keffel ◽  
Mark Goepel ◽  
Martin C. Michel
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Stimulation Of

scholarly journals Activation of the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway by Conventional, Novel, and Atypical Protein Kinase C Isotypes

1998 ◽  
Vol 18 (2) ◽  
pp. 790-798 ◽  
Author(s):  
Dorothee C. Schönwasser ◽  
Richard M. Marais ◽  
Christopher J. Marshall ◽  
Peter J. Parker
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Mapk ◽  
Kinase C ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Stimulation Of

ABSTRACT Phorbol ester treatment of quiescent Swiss 3T3 cells leads to cell proliferation, a response thought to be mediated by protein kinase C (PKC), the major cellular receptor for this class of agents. We demonstrate here that this proliferation is dependent on the activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) cascade. It is shown that dominant-negative PKC-α inhibits stimulation of the ERK/MAPK pathway by phorbol esters in Cos-7 cells, demonstrating a role for PKC in this activation. To assess the potential specificity of PKC isotypes mediating this process, constitutively active mutants of six PKC isotypes (α, β1, δ, ɛ, η, and ζ) were employed. Transient transfection of these PKC mutants into Cos-7 cells showed that members of all three groups of PKC (conventional, novel, and atypical) are able to activate p42 MAPK as well as its immediate upstream activator, the MAPK/ERK kinase MEK-1. At the level of Raf, the kinase that phosphorylates MEK-1, the activation cascade diverges; while conventional and novel PKCs (isotypes α and η) are potent activators of c-Raf1, atypical PKC-ζ cannot increase c-Raf1 activity, stimulating MEK by an independent mechanism. Stimulation of c-Raf1 by PKC-α and PKC-η was abrogated for RafCAAX, which is a membrane-localized, partially active form of c-Raf1. We further established that activation of Raf is independent of phosphorylation at serine residues 259 and 499. In addition to activation, we describe a novel Raf desensitization induced by PKC-α, which acts to prevent further Raf stimulation by growth factors. The results thus demonstrate a necessary role for PKC and p42 MAPK activation in 12-O-tetradecanoylphorbol-13-acetate induced mitogenesis and provide evidence for multiple PKC controls acting on this MAPK cascade.

MEK5/ERK5: Mitogen-Activated Protein Kinase 5/Extracellular Signal-Regulated Kinase 5

2012 ◽  
pp. 1074-1074
Author(s):  
Andreas Gewies ◽  
Jürgen Ruland ◽  
Alexey Kotlyarov ◽  
Matthias Gaestel ◽  
Shiri Procaccia ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein
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