TI  - The cytokine-activated tyrosine kinase  <prot>JAK2</prot>  activates  <prot>Raf-1</prot>  in a
      <prot>p21ras</prot>-dependent manner.
PG  - 11681-6
AB  -  <prot>JAK2</prot> , a member of the Janus kinase superfamily was found to interact
      functionally with  <prot>Raf-1</prot> , a central component of the <prot>ras</prot>/<prot>mitogen-activated
      protein kinase</prot> signal transduction pathway.   <prot>Interferon-gamma</prot>   and several
      other cytokines that are known to activate  <prot><prot>JAK2</prot> kinase</prot>  were also found to
      stimulate   <prot><prot>Raf-1</prot> kinase</prot>   activity toward  <prot>MEK-1</prot>  in mammalian cells. In the
      baculovirus coexpression system,  <prot>Raf-1</prot>  was activated by  <prot>JAK2</prot>  in the
      presence of  <prot>p21ras</prot> . Under these conditions, a ternary complex of  <prot>p21ras</prot> ,
       <prot>JAK2</prot> , and  <prot>Raf-1</prot>  was observed. In contrast, in the absence of <prot>p21ras</prot>,
      coexpression of <prot>JAK2</prot> and <prot>Raf-1</prot> resulted in an overall decrease in the
      <prot>Raf-1</prot> kinase activity. In addition,  <prot>JAK2</prot>  phosphorylated   <prot>Raf-1</prot>   at sites
      different from those phosphorylated by  <prot>pp60v-src</prot> . In mammalian cells
      treated with either erythropoietin or interferon-gamma, a small fraction
      of  <prot>Raf-1</prot>  coimmunoprecipitated with  <prot>JAK2</prot>  in lysates of cells in which <prot>JAK2</prot>
      was activated as judged by its state of tyrosine phosphorylation. Taken
      together, these data suggest that <prot>JAK2</prot> and <prot>p21ras</prot> cooperate to activate
      <prot>Raf-1</prot>.
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
