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Molecular and Cellular Biology, November 1998, p. 6795-6804, Vol. 18, No. 11
Integrated Program in Molecular,
Received 4 February 1998/Returned for modification 30 March
1998/Accepted 23 July 1998
In Abelson murine leukemia virus (A-MuLV)-transformed cells,
members of the Janus kinase (Jak) family 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.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Direct Interaction of Jak1 and v-Abl Is Required
for v-Abl-Induced Activation of STATs and
Proliferation
*
Corresponding author. Mailing address: Department of
Medicine/Microbiology, Columbia University, 630 W. 168th St., New York, NY 10032-3702. Phone: (212) 305-6982. Fax: (212) 205-1870. E-mail: pbr3{at}columbia.edu.
Molecular and Cellular Biology, November 1998, p. 6795-6804, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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