JAK-STAT SIGNALING INDUCED BY THE V-ABL ONCOGENE

The effect of the v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) on the Jak-STAT pathway of cytokine signal transduction was investigated. In murine pre-B lymphocytes transformed with A-MuLV, the Janus kinases (Jaks) Jak1 and Jak3 exhibited constitutive tyrosine kinase activity, acid the STAT proteins (signal transducers and activators of transcription) normally activated by interleukin-4, and interleukin-7 were tyrosine-phosphorylated in the absence of these cytokines. Coimmunoprecipitation experiments revealed that in these cells v-Abl was physically associated with Jak1 and Jak3. Inactivation of v-Abl tyrosine kinase in a pre-B cell line transformed with a temperature-sensitive mutant of v-abl resulted in abrogation of constitutive Jak-STAT signaling. A direct link may exist between transformation by v-abl and cytokine signal transduction.