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JAK-STAT signaling activated by Abl oncogenes

Oncogene volume 19, pages 2523–2531 (2000)Cite this article

Abstract

The Abl oncoproteins v-Abl and BCR-Abl 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.

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Acknowledgements

We would like to acknowledge our collaboration with Drs Stephen Goff and Kathryn Calame at Columbia University, Naomi Rosenberg (Tufts University), and Jean Wang (UC San Diego) in the Abl field, and Christian Schindler (Columbia University) in the JAK-STAT field. This work has been supported by The Leukemia Society of America, Cancer Research Institute, and by the National Cancer Institute.

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  1. Department of Microbiology, Integrated Program in Molecular, Cellular and Biophysical Studies, College of Physicians and Surgeons of Columbia University, 630 168th Street West, New York, 10032, NY, USA

    Nika N Danial & Paul Rothman

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Danial, N., Rothman, P. JAK-STAT signaling activated by Abl oncogenes. Oncogene 19, 2523–2531 (2000). https://doi.org/10.1038/sj.onc.1203484

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