TEC AND JAK2 KINASES COOPERATE TO MEDIATE CYTOKINE-DRIVEN ACTIVATION OF C-FOS TRANSCRIPTION

Although transcriptional activation of the c-fos protooncogene plays a n intrinsic role in the mechanism of blood cell growth, it is still ob scure how protein-tyrosine kinases (PTKs) regulate the cytokine-driven c-fos activation pathway. We present here that Tec PTK is tyrosine-ph osphorylated and activated by granulocyte-macrophage colony-stimulatin g factor (GM-CSF) stimulation in a human GM-CSF-dependent cell line. M oreover, we could show that introduction of Tec into mouse BA/F3-hGMR alpha beta cells can profoundly activate the c-fos promoter in respons e to GM-CSF or to interleukin-3 (IL-3). In contrast, introduction of a kinase-deleted Tec could suppress cytokine-driven c-fos activation, i ndicating that Tec is directly involved in the regulation of c-fos tra nscription. Interestingly, strong activation by Tec of the c-fos promo ter was blocked by the co-expression of dominant negative Jak2. The mo lecular interaction between Tec and Jak2 was then investigated both in mammalian and insect cell systems, revealing that they can not only b ind to each other, but either of the two can phosphorylate the other, Thus, Tec and Jak2 can ''cross-talk'' in a complexed way to mediate cy tokine-driven c-fos activation. (C) 1998 by The American Society of He matology.