Mitogenic regulation of polyamine biosynthesis by increases in mRNA level and efficiency of translation
Within 1-2 h after stimulation of T-lymphocytes with concanavalin A (ConA), both S-adenosylmethionine decarboxylase (SDC) and ornithine decarboxylase (ODC) mRNAs are elevated. The phorbol esters, 12-0-tetradecanoylphorbol 13-acetate (TPA) or phorbol 12,13-dibutyrate, increased ODC mRNA in the same time frame and to the same magnitude as ConA, but were not by themselves mitogenic. In contrast to ConA, the phorbol esters alone were without effect on the resting level of c-myc mRNA. Thus, these results suggest that elevation of ODC mRNA by ConA is through activation of a protein kinase C linked pathway, while that of c-myc is not. Comparisons of mRNA levels with changes in either synthetic rate or activity of ODC and SDC revealed 2-fold and 5-fold discrepancies, respectively. ODC and SDC mRNAs shift into larger polysomes after ConA addition, demonstrating an increase in efficiency of translation. This change in translational efficiency is not generally true of all message species, since the size of polysomes containing actin or c-myc mRNAs was identical in resting and activated cells. In conclusion modulation of the key regulatory steps of polyamine biosynthesis during lymphocyte mitogenesis is controlled at two levels: 1.) regulation of mRNA increases mediated by a pathway involving activation of protein kinase C and 2.) control of mRNA translational efficiency mediated through changes in initiation.
- Research Organization:
- Univ. of Washington, Seattle
- OSTI ID:
- 5243200
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINES
BIOSYNTHESIS
CONCANAVALIN
BIOLOGICAL EFFECTS
DECARBOXYLASES
ENZYME ACTIVITY
PHORBOL ESTERS
BIOLOGICAL PATHWAYS
LYMPHOCYTES
MESSENGER-RNA
MITOGENS
PHOSPHOTRANSFERASES
SYNERGISM
AGGLUTININS
ANIMAL CELLS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBON-CARBON LYASES
CARBOXY-LYASES
CARCINOGENS
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
HEMAGGLUTININS
LECTINS
LEUKOCYTES
LYASES
MATERIALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
RNA
SOMATIC CELLS
SYNTHESIS
TRANSFERASES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)