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- W1901001479 endingPage "2462" @default.
- W1901001479 startingPage "2452" @default.
- W1901001479 abstract "Abstract M-CSF triggers the activation of extracellular signal-regulated protein kinases (ERK)-1/2. We show that inhibition of this pathway leads to the arrest of bone marrow macrophages at the G0/G1 phase of the cell cycle without inducing apoptosis. M-CSF induces the transient expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), which correlates with the inactivation of ERK-1/2. Because the time course of ERK activation must be finely controlled to induce cell proliferation, we studied the mechanisms involved in the induction of MKP-1 by M-CSF. Activation of ERK-1/2 is not required for this event. Therefore, M-CSF activates ERK-1/2 and induces MKP-1 expression through different pathways. The use of two protein kinase C (PKC) inhibitors (GF109203X and calphostin C) revealed that M-CSF induces MKP-1 expression through a PKC-dependent pathway. We analyzed the expression of different PKC isoforms in bone marrow macrophages, and we only detected PKCβI, PKCε, and PKCζ. PKCζ is not inhibited by GF109203X/calphostin C. Of the other two isoforms, PKCε is the best candidate to mediate MKP-1 induction. Prolonged exposure to PMA slightly inhibits MKP-1 expression in response to M-CSF. In bone marrow macrophages, this treatment leads to a complete depletion of PKCβI, but only a partial down-regulation of PKCε. Moreover, no translocation of PKCβI or PKCζ from the cytosol to particulate fractions was detected in response to M-CSF, whereas PKCε was constitutively present at the membrane and underwent significant activation in M-CSF-stimulated macrophages. In conclusion, we remark the role of PKC, probably isoform ε, in the negative control of ERK-1/2 through the induction of their specific phosphatase." @default.
- W1901001479 created "2016-06-24" @default.
- W1901001479 creator A5024300705 @default.
- W1901001479 creator A5024628680 @default.
- W1901001479 creator A5041310234 @default.
- W1901001479 creator A5057779456 @default.
- W1901001479 date "1999-09-01" @default.
- W1901001479 modified "2023-10-18" @default.
- W1901001479 title "Macrophage Colony-Stimulating Factor Induces the Expression of Mitogen-Activated Protein Kinase Phosphatase-1 Through a Protein Kinase C-Dependent Pathway" @default.
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- W1901001479 doi "https://doi.org/10.4049/jimmunol.163.5.2452" @default.
- W1901001479 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10452980" @default.
- W1901001479 hasPublicationYear "1999" @default.
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