CONSTITUTIVE ACTIVATION OF THE JANUS KINASE STAT PATHWAY IN T-LYMPHOMA OVEREXPRESSING THE LCK PROTEIN-TYROSINE KINASE

The Lck protein, a Src family tyrosine kinase, plays a critical role i n T cell maturation and activation. Dysregulation of Lck expression or Lck kinase activity has been implicated in T cell leukemias from mice to humans, although the mechanism underlying Lck-mediated oncogenesis is still largely unclear. We report here that both DNA binding activi ties and tyrosine phosphorylation of STAT3 and STAT5, but not STAT1, a re constitutively enhanced in the mouse T cell lymphoma LSTRA, which i s a well-characterized cell line that overexpresses Lck protein and ex hibits high levels of Lck kinase activity, Furthermore, Janus kinase 1 (Jak1) and Jak2 protein tyrosine kinases are constantly activated in these cells, as determined by their autophosphorylation in an in vitro kinase assay and increased levels of tyrosine phosphorylation on immu noblots. Therefore, like Src-transformed cells, Lck-overexpressing LST RA cells also exhibit constitutive activation of distinct Jak and STAT proteins.