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PMID: 7813438 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Altering the specificity of signal transduction cascades: positive regulation of c-Jun transcriptional activity by protein kinase A.

The EMBO journal ·Vol. 13 ·No. 24 ·1994-12-15 ·Pages 6006-10

Smeal T, Hibi M, Karin M

Abstract

Protein phosphorylation is commonly used to modulate transcription factor activity. However, all existing genetic evidence for stimulation of transcription factor activity by phosphorylation rests on loss-of-function mutations. To demonstrate conclusively that phosphorylation of a transcription factor potentiates its transactivation potential in vivo, we constructed a c-Jun mutant that is phosphorylated by the cAMP-sensitive protein kinase A (PKA) instead of the UV- and Ras-responsive protein kinase JNK. The transcriptional activity of this mutant is enhanced by PKA, but not by JNK activation. These results provide a positive and conclusive proof that phosphorylation of c-Jun on a critical site (Ser73) located in its activation domain is directly responsible for enhancing its transactivation function.

MeSH Terms
Amino Acid Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases Molecular Sequence Data Mutagenesis, Site-Directed Phosphorylation Proto-Oncogene Proteins c-jun/genetics,metabolism Recombinant Proteins/metabolism Signal Transduction Substrate Specificity Transcription, Genetic Transcriptional Activation
Chemicals
Proto-Oncogene Proteins c-jun Recombinant Proteins Cyclic AMP-Dependent Protein Kinases Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Smeal T
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
Hibi M
Karin M
References (27)
27 references, click to expand
  1. Oncoprotein-mediated signalling cascade stimulates c-Jun activity by phosphorylation of serines 63 and 73.
    Mol Cell Biol. 1992 Aug;12(8):3507-13 PMID: 1630458
  2. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.
    Cell. 1994 Mar 25;76(6):1025-37 PMID: 8137421
  3. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain.
    Genes Dev. 1993 Nov;7(11):2135-48 PMID: 8224842
  4. The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases.
    Cell. 1992 Dec 24;71(7):1081-91 PMID: 1473146
  5. Control of transcription factors by signal transduction pathways: the beginning of the end.
    Trends Biochem Sci. 1992 Oct;17(10):418-22 PMID: 1455510
  6. v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor.
    Nature. 1991 Jul 11;352(6331):165-8 PMID: 1906140
  7. Phosphorylated CREB binds specifically to the nuclear protein CBP.
    Nature. 1993 Oct 28;365(6449):855-9 PMID: 8413673
  8. Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity.
    Cell. 1992 Sep 4;70(5):777-89 PMID: 1516134
  9. Activation of cAMP and mitogen responsive genes relies on a common nuclear factor.
    Nature. 1994 Jul 21;370(6486):226-9 PMID: 8028671
  10. Regulating transcription factor activity by phosphorylation.
    Trends Cell Biol. 1992 Apr;2(4):104-8 PMID: 14732014
  11. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain.
    Cell. 1993 Apr 23;73(2):381-93 PMID: 8386592
  12. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.
    Cell. 1989 Nov 17;59(4):675-80 PMID: 2573431
  13. Signal transduction from the cell surface to the nucleus through the phosphorylation of transcription factors.
    Curr Opin Cell Biol. 1994 Jun;6(3):415-24 PMID: 7917334
  14. Expression of the catalytic subunit of cAMP-dependent protein kinase in Escherichia coli.
    J Biol Chem. 1989 Dec 15;264(35):20940-6 PMID: 2687267
  15. Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain.
    Nature. 1993 Aug 5;364(6437):544-7 PMID: 8336793
  16. The regulation of transcription by phosphorylation.
    Cell. 1992 Aug 7;70(3):375-87 PMID: 1643656
  17. An adenosine 3',5'-monophosphate-dependant protein kinase from rabbit skeletal muscle.
    J Biol Chem. 1968 Jul 10;243(13):3763-5 PMID: 4298072
  18. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
    Cell. 1987 Jun 19;49(6):729-39 PMID: 3034432
  19. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73.
    Nature. 1991 Dec 12;354(6353):494-6 PMID: 1749429
  20. Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity.
    Cell. 1991 Feb 8;64(3):573-84 PMID: 1846781
  21. Signal transduction from cell surface to nucleus in development and disease.
    FASEB J. 1992 May;6(8):2581-90 PMID: 1317309
  22. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain.
    Nature. 1991 May 9;351(6322):122-7 PMID: 1903181
  23. Protein kinase recognition sequence motifs.
    Trends Biochem Sci. 1990 Sep;15(9):342-6 PMID: 2238044
  24. Rapid and reversible translocation of the catalytic subunit of cAMP-dependent protein kinase type II from the Golgi complex to the nucleus.
    EMBO J. 1985 Nov;4(11):2801-6 PMID: 2998755
  25. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.
    Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 PMID: 1751545
  26. Phosphorylation of c-jun mediated by MAP kinases.
    Nature. 1991 Oct 17;353(6345):670-4 PMID: 1922387
  27. Recombinant cyclic AMP response element binding protein (CREB) phosphorylated on Ser-133 is transcriptionally active upon its introduction into fibroblast nuclei.
    J Biol Chem. 1994 Mar 11;269(10):7623-30 PMID: 8125987
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-12-15
Pages
6006-10
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395577
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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