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J Biol Chem, Vol. 275, Issue 17, 12963-12969, April 28, 2000
From the Department of Cellular and Molecular Biology and Cancer
Center, Northwestern University Medical School,
Chicago, Illinois 60611-3008
Activation of protein kinase C (PKC) and protein
kinase A (PKA) in rat C6 glioma cells increases the half-life of
short-lived lactate dehydrogenase (LDH)-A mRNA about 5- and 8-fold,
respectively. PKA and PKC act synergistically and prolong LDH-A
mRNA half-life more than 21-fold. Similar effects were observed
after transfection and transcription of a globin/lactate dehydrogenase
minigene consisting of a
Structural Determinants for Post-transcriptional
Stabilization of Lactate Dehydrogenase A mRNA by the Protein
Kinase C Signal Pathway*
-globin expression vector in which the
3'-untranslated region (UTR) of -globin had been replaced with the
LDH-A 3'-UTR. Synergism was only obtained by transcription of minigenes
containing the entire 3'-UTR and did not occur when truncated 3'-UTR
fragments were analyzed. Additional mutational analyses showed that a
20-nucleotide region, named PKC-stabilizing region (PCSR), is
responsible for mediating the stabilizing effect of PKC. Previous
studies (Tian, D., Huang, D., Short, S., Short, M. L., and
Jungmann, R. A. (1998) J. Biol. Chem. 273, 24861-24866) have demonstrated the existence of a cAMP-stabilizing
region in LDH-A 3'-UTR. Sequence analysis of PCSR identified a
13-nucleotide AU-rich region that is common to both cAMP-stabilizing
region and PCSR. These studies identify a specific PKC-responsive
stabilizing element and indicate that interaction of PKA and PKC
results in a potentiating effect on LDH-A mRNA stabilization.
*
This work was supported by Grant GM53115 from the National
Institutes of Health and Neuroscience Training Grant T32NS07140 (to
D. T.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Cell and
Molecular Biology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Tel.: 312-908-5275; Fax: 312-503-7107; E-mail: rjungman@nwu.edu.
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