Glycated Serum Albumin-Induced Vascular Smooth Muscle Cell Proliferation through Activation of the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway by Protein Kinase C

2001 ◽  
Vol 282 (3) ◽  
pp. 850-851
Author(s):  
Yoshiyuki Hattori ◽  
Hirobumi Kakishita ◽  
Kazumi Akimoto ◽  
Mihoko Matsumura ◽  
Kikuo Kasai
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

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.

Targeted degradation of ENaC in response to PKC activation of the ERK1/2 cascade

2003 ◽  
Vol 284 (5) ◽  
pp. F938-F947 ◽  
Author(s):  
Rachell E. Booth ◽  
James D. Stockand
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Actinomycin D ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Extracellular Signal ◽  
Pkc Signaling ◽  
Mitogen Activated Protein ◽  
Pkc Activation

Renal A6 epithelial cells were used to determine the mechanism by which protein kinase C (PKC) decreases epithelial Na+ channel (ENaC) activity. Activation of PKC reduced relative Na+ reabsorption to <20% within 60 min. This decrease was sustained over the next 24–48 h. In response to PKC signaling, α-, β-, and γ-ENaC levels were 0.97, 0.36, and 0.39, respectively, after 24 h, with the levels of the latter two subunits being significantly decreased. The PKC-mediated decreases in β- and γ-ENaC were significantly reversed by simultaneous addition of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase-1/2 inhibitors U-0126 and PD-98059. These inhibitors, in addition, protected Na+ reabsorption from PKC, demonstrating that the MAPK1/2 cascade, in some instances, plays a central role in downregulation of ENaC activity. The effects of PKC on β- and γ-ENaC levels were additive with those of inhibitors of transcription (actinomycin D) and translation (emetine and cycloheximide), suggesting that PKC promotes subunit degradation and does not affect subunit synthesis. The bulk of whole cell γ-ENaC was degraded within 1 h after treatment with inhibitors of synthesis; however, a significant pool was “protected” from inhibitors for up to 12 h. PKC affected this protected pool of γ-ENaC. Moreover, proteosome inhibitors (MG-132 and lactacystin) reversed PKC effects on this protected pool of γ-ENaC. Thus PKC signaling via MAPK1/2 cascade activation in A6 cells promotes degradation of γ-ENaC.

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