Cell growth inhibition by all-trans retinoic acid in SKBR-3 breast cancer cells: Involvement of protein kinase C? and extracellular signal-regulated kinase mitogen-activated protein kinase

2003 ◽  
Vol 38 (3) ◽  
pp. 106-116 ◽  
Author(s):  
Shino Nakagawa ◽  
Teruhiko Fujii ◽  
Goro Yokoyama ◽  
Marcelo G. Kazanietz ◽  
Hideaki Yamana ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Breast Cancer Cells ◽  
Mitogen Activated Protein Kinase ◽  
Cell Growth Inhibition ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

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.

scholarly journals Protein kinase C (PKC)-δ/-ε mediate the PKC/Akt-dependent phosphorylation of extracellular signal-regulated kinases 1 and 2 in MCF-7 cells stimulated by bradykinin

2006 ◽  
Vol 188 (1) ◽  
pp. 79-89 ◽  
Author(s):  
S Greco ◽  
C Storelli ◽  
S Marsigliante
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Breast Cancer Cells ◽  
Mitogen Activated Protein Kinase ◽  
Kinase C ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase ◽  
Mcf 7 ◽  
Protein Kinase Kinase

In this paper the signal transduction pathways evoked by bradykinin (BK) in MCF-7 breast cancer cells were investigated. BK activation of the B2 receptor provoked: (a) the phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2); (b) the translocation from the cytosol to the membrane of the conventional protein kinase C-α (PKC-α) and novel PKC-δ and PKC-ε; (c) the phosphorylation of protein kinase B (PKB/ Akt); (d) the proliferation of MCF-7 cells. The BK-induced ERK1/2 phosphorylation was completely blocked by PD98059 (an inhibitor of the mitogen-activated protein kinase kinase (MAPKK or MEK)) and by LY294002 (an inhibitor of phosphoinositide 3-kinase (PI3K)), and was reduced by GF109203X (an inhibitor of both novel and conventional PKCs); Gö6976, a conventional PKCs inhibitor, did not have any effect. The BK-induced phosphorylation of PKB/Akt was blocked by LY294002 but not by PD98059. Furthermore, LY294002 inhibited the BK-provoked translocation of PKC-δ and PKC-ε suggesting that PI3K may be upstream to PKCs. Finally, the proliferative effects of BK were blocked by PD98059, GF109203X and LY294002. These observations demonstrate that BK acts as a proliferative agent in MCF-7 cells activating intracellular pathways involving novel PKC-δ/-ε, PKB/Akt and ERK1/2.

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