c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases

Audrey Minden, Anning Lin, Tod Smeal, Benoit Dérijard, Melanie Cobb, Roger Davis, Michael Karin

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Abstract

c-Jun transcriptional activity is stimulated by phosphorylation at two N- terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli, including growth factors, cytokines, and UV irradiation. New members of the mitogen-activated protein (MAP) kinase group of signal-transducing enzymes, termed JNKs, bind to the activation domain of c-Jun and specifically phosphorylate these sites. However, the N-terminal sites of c-Jun were also suggested to be phosphorylated by two other MAP kinases, ERK1 and ERK2. Despite these reports, we find that unlike the JNKs, ERK1 and ERK2 do not phosphorylate the N-terminal sites of c-Jun in vitro; instead they phosphorylate an inhibitory C-terminal site. Furthermore, the phosphorylation of c-Jun in vivo at the N- terminal sites correlates with activation of the JNKs but not the ERKs. The ERKs are probably involved in the induction of c-fos expression and thereby contribute to the stimulation of AP-1 activity. Our study suggests that two different branches of the MAP kinase group are involved in the stimulation of AP-1 activity through two different mechanisms.

Original languageEnglish (US)
Pages (from-to)6683-6688
Number of pages6
JournalMolecular and Cellular Biology
Volume14
Issue number10
StatePublished - Oct 1994

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Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Phosphorylation
Intercellular Signaling Peptides and Proteins
Cytokines
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases. / Minden, Audrey; Lin, Anning; Smeal, Tod; Dérijard, Benoit; Cobb, Melanie; Davis, Roger; Karin, Michael.

In: Molecular and Cellular Biology, Vol. 14, No. 10, 10.1994, p. 6683-6688.

Research output: Contribution to journalArticle

Minden, Audrey ; Lin, Anning ; Smeal, Tod ; Dérijard, Benoit ; Cobb, Melanie ; Davis, Roger ; Karin, Michael. / c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases. In: Molecular and Cellular Biology. 1994 ; Vol. 14, No. 10. pp. 6683-6688.
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AU - Cobb, Melanie

AU - Davis, Roger

AU - Karin, Michael

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