ACTIVATION OF THE JAK STAT PATHWAY LEADS TO PROLIFERATION OF ST14A CENTRAL-NERVOUS-SYSTEM PROGENITOR CELLS/

We were interested in whether central nervous system progenitor cells possess the signal transduction machinery necessary to mediate cytokin e functions and whether this machinery can become activated upon stabl e expression of a particular cytokine receptor. For this purpose we ut ilized a previously obtained conditionally immortalized striatum-deriv ed nestin-positive cell. line (ST14A). We found that ST14A cells expre ss Jak2, but not Jak1 or Tyk2. An identical pattern of expression was found in embryonic striatal tissue. To evaluate the susceptibility of these cytokine specific cytoplasmic transducers to activation, ST14A c ells were stably transfected with the alpha and beta (AIC2A) chains of the murine interleukin-3 receptor. Four independent lines expressing both the alpha and beta receptor subunits were obtained. We found that cells from each of these lines were induced to proliferate upon expos ure to interleukin-3. Dose response curve, antibody blocking experimen ts and binding studies revealed that the response was mediated by the reconstituted high affinity interleukin-3 receptor. Immunoprecipitatio n studies on these cells showed that Jak2 and Stat5 were being phospho rylated after stimulation of the reconstituted receptor. These results indicate that members of the JAK/STAT family of proteins are expresse d in central nervous system progenitor cells and are susceptible to ac tivation through stimulation of an exogenously expressed cytokine rece ptor, ultimately leading to cell proliferation.