Direct interaction of Jak1 and v-Abl is required for v-Abl-induced activation of STATs and proliferation

Nika N. Danial, Julie A. Losman, Tianhong Lu, Natalie Yip, Kartik Krishnan, John Krolewski, Stephen P. Goff, Jean Y.J. Wang, Paul B. Rothman

Research output: Contribution to journalArticlepeer-review

Abstract

In Abelson murine leukemia virus (A-MuLV)-transformed cells, members of the Janus kinase (Jak) fammily of non-receptor tyrosine kinases and the signal transducers and activators of transcription (STAT) family of signaling proteins are constitutively activated. In these cells, the v-Abl oncoprotein and the Jak proteins physically associate. To define the molecular mechanism of constitutive Jak-STAT signaling in these cells, the functional significance of the v-Abl-Jak association was examined. Mapping the Jak1 interaction domain in v-Abl demonstrates that amino acids 858 to 1080 within the carboxyl-terminal region of v-Abl bind Jak1 through a direct interaction. A mutant of v-Abl lacking this region exhibits a significant defect in Jak1 binding in vivo, fails to activate Jak1 and STAT proteins, and does not support either the proliferation or the survival of BAF/3 cells in the absence of cytokine. Cells expressing this v-Abl mutant show extended latency and decreased frequency in generating tumors in nude mice. In addition, inducible expression of a kinase-inactive mutant of Jak1 protein inhibits the ability of v-Abl to activate STATs and to induce cytokine-independent proliferation, indicating that an active Jak1 is required for these v-Abl- induced signaling pathways in vivo. We propose that Jak1 is a mediator of v- Abl-induced STAT activation and v-Abl induced proliferation in BAF/3 cells, and may be important for efficient transformation of immature B cells by the v-abl oncogene.

Original languageEnglish (US)
Pages (from-to)6795-6804
Number of pages10
JournalMolecular and cellular biology
Volume18
Issue number11
DOIs
StatePublished - Nov 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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