Abstract
The mitogen-activated protein kinases (MAPKs) ERK-1 and ERK-2 are activated by a wide variety of oncogenes and extracellular stimuli. The MAPKs participate in a signalling cascade downstream of growth factor/cytokine receptors, Ras, Raf, and MEK. However, MAPK activation is more complicated than a simple linear pathway, and the evidence presented here supports a model of multiple, temporally distinct pathways converging on MAPK which are differentially utilized by various stimuli and cell types. In addition to MEK-dependent MAPK activation, we provide evidence for MEK-independent regulation of the MAPKs. Our results suggest that phosphatidylinositol-3-kinases (PI(3)K) or conventional protein kinase C isoforms (cPKCs) partially contribute to MEK-dependent activation. Importantly, we also find that PI3K and cPKCs play a major role in the MEK-independent, prolonged MAPK activation by platelet-derived growth factor signalling. This finding is of interest as the maintained activation of MAPK has been correlated by others to the regulation of cell proliferation and differentiation.
MeSH terms
-
3T3 Cells
-
Androstadienes / pharmacology
-
Animals
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
-
Down-Regulation
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology
-
Flavonoids / pharmacology
-
MAP Kinase Kinase 1
-
Mice
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinase Kinases*
-
Mitogen-Activated Protein Kinases*
-
Phosphatidylinositol 3-Kinases
-
Phosphorylation
-
Phosphotransferases (Alcohol Group Acceptor) / metabolism
-
Platelet-Derived Growth Factor / pharmacology
-
Protein Kinase C / metabolism
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein Serine-Threonine Kinases / metabolism*
-
Protein-Tyrosine Kinases / antagonists & inhibitors
-
Protein-Tyrosine Kinases / metabolism*
-
Ribosomal Protein S6 Kinases
-
Signal Transduction
-
Wortmannin
Substances
-
Androstadienes
-
Enzyme Inhibitors
-
Flavonoids
-
Platelet-Derived Growth Factor
-
Phosphotransferases (Alcohol Group Acceptor)
-
Protein-Tyrosine Kinases
-
Protein Serine-Threonine Kinases
-
Ribosomal Protein S6 Kinases
-
Protein Kinase C
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 1
-
Map2k1 protein, mouse
-
Mitogen-Activated Protein Kinase Kinases
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
-
Wortmannin