Involvement of Ca/sup 2 +//phospholipid-dependent C-kinase in phorbol ester-mediated activation of normal human T cell
C-kinase appears to be involved in biological responses of T cells, and phorbol myristate acetate (PMA) is a direct activator of this enzyme. In this study, reaction of T cells with PMA (0.1-50 ng/ml) showed a dose-dependent increase in /sup 3/H-thymidine incorporation; higher concentrations were toxic. C-kinase assays performed in parallel demonstrated sustained translocation of >99% of C-kinase activity from the cytosol to the detergent-soluble membrane fraction. Experiments were done in the presence of cyclosporine (CSA), and of polymyxin B (PMB) which also inhibits C-kinase. Both PMA and CSA caused profound and dose-dependent reduction in proliferation, with maximal inhibition of >70% and >90% respectively. Moreover, addition of PMB showed coordinate inhibition of C-kinase activity (>80% at 10 ..mu..M), whereas at similar concentrations inhibiting cell proliferation CSA had no detectable effect. These results indicate that PMA initiates activation and proliferation by stimulation of at least two distinct pathways, one of which involves C-kinase activation and is inhibited by PMB.
- Research Organization:
- Medical Univ. of South Carolina, Charleston
- OSTI ID:
- 5388089
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
Similar Records
Cyclosporin A does not block the phorbol ester - protein kinase C regulated pathway of T cell activation
Activation of Ca/sup 2 +//phospholipid-dependent C-kinase upon interaction of human T cells with stimulatory ligands
Related Subjects
LYMPHOCYTES
CELL PROLIFERATION
PHORBOL ESTERS
TOXICITY
PHOSPHOTRANSFERASES
ENZYME ACTIVITY
BIOLOGICAL PATHWAYS
CALCIUM
CELL MEMBRANES
DOSE-RESPONSE RELATIONSHIPS
INHIBITION
PEPTIDES
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALINE EARTH METALS
ANIMAL CELLS
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
ELEMENTS
ENZYMES
ESTERS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
MATERIALS
MEMBRANES
METALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
PYRIMIDINES
RIBOSIDES
SOMATIC CELLS
TRANSFERASES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)