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Evidence for Protein Kinase C-Dependent and -Independent Activation of Mitogen-Activated Protein Kinase in T Cells: Potential Role of Additional Diacylglycerol Binding Proteins
- Source :
- The Journal of Immunology. 165:6865-6871
- Publication Year :
- 2000
- Publisher :
- The American Association of Immunologists, 2000.
-
Abstract
- Activation of mitogen-activated protein kinases (MAPK) is a critical signal transduction event for CTL activation, but the signaling mechanisms responsible are not fully characterized. Protein kinase C (PKC) is thought to contribute to MAPK activation following TCR stimulation. We have found that dependence on PKC varies with the method used to stimulate the T cells. Extracellular signal-regulated kinase (ERK) activation in CTL stimulated with soluble cross-linked anti-CD3 is completely inhibited by the PKC inhibitor bisindolylmaleimide (BIM). In contrast, only the later time points in the course of ERK activation are sensitive to BIM when CTL are stimulated with immobilized anti-CD3, a condition that stimulates CTL degranulation. Surprisingly, MAPK activation in response to immobilized anti-CD3 is strongly inhibited at all time points by the diacylglycerol (DAG)-binding domain inhibitor calphostin C implicating the contribution of a DAG-dependent but PKC-independent pathway in the activation of ERK in CTL clones. Chronic exposure to phorbol ester down-regulates the expression of DAG-responsive PKC isoforms; however, this treatment of CTL clones does not inhibit anti-CD3-induced activation of MAPK. Phorbol ester-treated cells have reduced expression of several isoforms of PKC but still express the recently described DAG-binding Ras guanylnucleotide-releasing protein. These results indicate that the late phase of MAPK activation in CTL clones in response to immobilized anti-CD3 stimulation requires PKC while the early phase requires a DAG-dependent, BIM-resistant component.
- Subjects :
- MAPK/ERK pathway
Indoles
Mitogen-Activated Protein Kinase 3
Immunology
Receptors, Antigen, T-Cell
Naphthalenes
Biology
Lymphocyte Activation
Cell Degranulation
Diglycerides
Maleimides
Mice
chemistry.chemical_compound
Animals
Immunology and Allergy
Antigens
Enzyme Inhibitors
Phosphorylation
Protein Kinase C
Protein kinase C
Diacylglycerol kinase
Mitogen-Activated Protein Kinase 1
Clone Cells
Protein Structure, Tertiary
Cell biology
Enzyme Activation
Mice, Inbred C57BL
Diacylglycerol binding
CTL
Calphostin C
chemistry
Mitogen-activated protein kinase
biology.protein
Interleukin-2
Tetradecanoylphorbol Acetate
Mitogen-Activated Protein Kinases
Muromonab-CD3
Protein Binding
Signal Transduction
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 165
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....990d0fffac6180b0781b513fb6d5df3b