Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell Biol
2005 Jun 01;2511:4676-82. doi: 10.1128/MCB.25.11.4676-4682.2005.
Show Gene links
Show Anatomy links
Graded mitogen-activated protein kinase activity precedes switch-like c-Fos induction in mammalian cells.
Mackeigan JP, Murphy LO, Dimitri CA, Blenis J.
???displayArticle.abstract???
The mitogen-activated protein kinase (MAPK) pathway is an evolutionarily conserved signaling module that controls important cell fate decisions in a variety of physiological contexts. During Xenopus oocyte maturation, the MAPK cascade converts an increasing progesterone stimulus into a switch-like, all-or-nothing response. While the importance of such switch-like behavior is widely discussed in the literature, it is not known whether the MAPK pathway in mammalian cells exhibits a switch-like or graded response. For this study, we used flow cytometry and immunofluorescence to generate single-cell measurements of MAPK signaling in Swiss 3T3 fibroblasts. In contrast to the case in Xenopus oocytes, we found that ERK activation in individual mammalian cells is not ultrasensitive and shows a graded response to changes in agonist concentration. Thus, the conserved MAPK signaling module exhibits different systems-level properties in different cellular contexts. Furthermore, the graded ERK response was converted into a more switch-like behavior at the level of immediate-early gene induction and cell cycle progression. Thus, while MAPK signaling is involved in all-or-nothing cell fate decisions for both Xenopus oocyte maturation and mammalian fibroblast proliferation, the underlying mechanisms responsible for the switch-like nature of the cellular responses are different in these two systems, with the mechanism appearing to lie downstream of the kinase cascade in mammalian fibroblasts.
Angeli,
Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems.
2004, Pubmed
Angeli,
Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems.
2004,
Pubmed Bagowski,
Bistability in the JNK cascade.
2001,
Pubmed
,
Xenbase Boulton,
ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF.
1991,
Pubmed Brunet,
Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry.
1999,
Pubmed Cantley,
The phosphoinositide 3-kinase pathway.
2002,
Pubmed Chen,
Nuclear localization and regulation of erk- and rsk-encoded protein kinases.
1992,
Pubmed Cobb,
ERKs, extracellular signal-regulated MAP-2 kinases.
1991,
Pubmed Ferrell,
How regulated protein translocation can produce switch-like responses.
1998,
Pubmed Ferrell,
The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes.
1998,
Pubmed
,
Xenbase Franke,
The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
1995,
Pubmed Luo,
Targeting the PI3K-Akt pathway in human cancer: rationale and promise.
2003,
Pubmed Murphy,
A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration.
2004,
Pubmed Murphy,
Molecular interpretation of ERK signal duration by immediate early gene products.
2002,
Pubmed Pomerening,
Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2.
2003,
Pubmed
,
Xenbase Roux,
Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.
2003,
Pubmed Seger,
Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.
1991,
Pubmed Sewing,
High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1.
1997,
Pubmed Whitehurst,
Stimulus-coupled spatial restriction of extracellular signal-regulated kinase 1/2 activity contributes to the specificity of signal-response pathways.
2004,
Pubmed Woods,
Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1.
1997,
Pubmed Yung,
Detection of ERK activation by a novel monoclonal antibody.
1997,
Pubmed
