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Jak-STAT signaling induced by the v-abl oncogene
N N Danial1, A Pernis, P B Rothman
1Integrated Program in Molecular, Cellular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Science (New York, N.Y.)
|September 29, 1995
Summary
The Abelson murine leukemia virus (A-MuLV) oncogene activates the Jak-STAT pathway in pre-B lymphocytes, leading to constitutive signaling. This study reveals a direct link between v-abl transformation and cytokine signal transduction.
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- The Janus kinase-STAT (Jak-STAT) pathway is crucial for cytokine signaling in immune cells.
- The v-abl oncogene from Abelson murine leukemia virus (A-MuLV) is known to cause lymphoid malignancies.
Purpose of the Study:
- To investigate the effect of the v-abl oncogene on the Jak-STAT pathway.
- To determine if v-abl transformation directly impacts cytokine signal transduction.
Main Methods:
- Studied murine pre-B lymphocytes transformed with A-MuLV.
- Utilized coimmunoprecipitation to assess protein interactions.
- Examined tyrosine kinase activity and phosphorylation of STAT proteins.
- Used a temperature-sensitive v-abl mutant to inactivate v-Abl tyrosine kinase.
Main Results:
- Constitutive tyrosine kinase activity of Jak1 and Jak3 was observed in A-MuLV-transformed cells.
- STAT proteins were tyrosine-phosphorylated independently of cytokines.
- v-Abl physically associated with Jak1 and Jak3.
- Inactivation of v-Abl kinase abrogated constitutive Jak-STAT signaling.
Conclusions:
- v-abl oncogene directly activates the Jak-STAT pathway.
- Transformation by v-abl is linked to dysregulation of cytokine signal transduction.
- This finding provides insight into the mechanisms of A-MuLV-induced leukemogenesis.