A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK

Daniela Barilá, Raffaella Mangano, Stefania Gonfloni, Jana Kretzschmar, Marina Moro, Dirk Bohmann, Giulio Superti-Furga

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The nuclear function of the c-Abl tyrosine kinase is not well understood. In order to identify nuclear substrates of Abl, we constructed a constitutively active and nuclear form of the protein. We found that active nuclear Abl efficiently phosphorylate c-Jun, a transcription factor not previously known to be tyrosine phosphorylated. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl. Surprisingly, elevated levels of c-Jun activated nuclear Abl, resulting in activation of the JNK serine/threonine kinase. This phosphorylation circuit generates nuclear tyrosine phosphorylation and represents a reversal of previously known signalling models.

Original languageEnglish
Pages (from-to)273-281
Number of pages9
JournalEMBO Journal
Volume19
Issue number2
Publication statusPublished - Jan 17 2000

Fingerprint

Phosphorylation
Tyrosine
Networks (circuits)
Substrates
MAP Kinase Kinase 4
src Homology Domains
Protein-Serine-Threonine Kinases
Nuclear Proteins
Protein-Tyrosine Kinases
Proteins
Transcription Factors
Chemical activation

Keywords

  • Abl
  • JNK
  • Jun
  • Nuclear tyrosine phosphorylation
  • Phosphorylation circuit

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Barilá, D., Mangano, R., Gonfloni, S., Kretzschmar, J., Moro, M., Bohmann, D., & Superti-Furga, G. (2000). A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK. EMBO Journal, 19(2), 273-281.

A nuclear tyrosine phosphorylation circuit : c-Jun as an activator and substrate of c-Abl and JNK. / Barilá, Daniela; Mangano, Raffaella; Gonfloni, Stefania; Kretzschmar, Jana; Moro, Marina; Bohmann, Dirk; Superti-Furga, Giulio.

In: EMBO Journal, Vol. 19, No. 2, 17.01.2000, p. 273-281.

Research output: Contribution to journalArticle

Barilá, D, Mangano, R, Gonfloni, S, Kretzschmar, J, Moro, M, Bohmann, D & Superti-Furga, G 2000, 'A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK', EMBO Journal, vol. 19, no. 2, pp. 273-281.
Barilá D, Mangano R, Gonfloni S, Kretzschmar J, Moro M, Bohmann D et al. A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK. EMBO Journal. 2000 Jan 17;19(2):273-281.
Barilá, Daniela ; Mangano, Raffaella ; Gonfloni, Stefania ; Kretzschmar, Jana ; Moro, Marina ; Bohmann, Dirk ; Superti-Furga, Giulio. / A nuclear tyrosine phosphorylation circuit : c-Jun as an activator and substrate of c-Abl and JNK. In: EMBO Journal. 2000 ; Vol. 19, No. 2. pp. 273-281.
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