JAK-STAT signaling activated by Abl oncogenes

Nika N. Danial, Paul Rothman

Research output: Contribution to journalReview article

Abstract

The Abl oncoproteins v-Abl and BCR-AM can activate member of the signal transducers and activators of transcription (STAT) family of signaling proteins. The mechanisms by which these oncoproteins activate STATs appear to differ. In cells transformed by v-Abl, Janus kinase (JAK) tyrosine kinases are constitutively activated. In these cells, the v-Abl oncoprotein and the JAK kinases physically associate. Mapping of the JAK interaction domain in v-Abl demonstrates that amino acids within the carboxyl terminal region of v-Abl bind JAKs through a direct interaction. A mutant of v-Abl lacking this region does not bind or activate JAK 1 in vivo, fails to activate STAT proteins, does not induce cellular proliferation, and is less efficient in cellular transformation. Kinase inactive mutants of JAK 1 inhibit the ability of v-Abl to activate STATs, to induce cytokine-independent proliferation, and to transform bone marrow cells. Interestingly, these effects correlate with defects in the activation of several pathways by v-Abl including Akt, PI3-kinase, STATs, and Ras. These data suggest that Jak kinases may play an important role in v-Abl induced transformation.

Original languageEnglish (US)
Pages (from-to)2523-2531
Number of pages9
JournalOncogene
Volume19
Issue number21
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • BCR-Abl
  • JAK
  • STAT
  • v-Abl

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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