Abstract
The protein tyrosine kinases JAK1, JAK2 and Tyk2 and STATs (signal transducers and activators of transcription) 1 and 3 are activated in response to interleukin-6 (IL-6) in human fibrosarcoma cells. In mutant cells lacking JAK1, JAK2 or Tyk2, the absence of one kinase does not prevent activation of the others; activation does not, therefore, involve a sequential three-kinase cascade. In the absence of JAK1, the phosphorylation of the gp130 subunit of the IL-6 receptor and the activation of STATs 1 and 3 are greatly reduced, JAK1 is also necessary for the induction of IRF1 mRNA, thus establishing a requirement for the JAK/STAT pathway in the IL-6 response. JAK2 and Tyk2 although activated cannot, in the absence of JAK1, efficiently mediate activation of STATs 1 and 3. A kinase-negative mutant of JAK2 can, however, inhibit such activation, and ancillary roles for JAK2 and Tyk2 are not excluded. A major role for JAK1 and the non-equivalence of JAK1 and JAK2 in the IL-6 response pathway are, nevertheless, clearly established for these cells.
Original language | English (US) |
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Pages (from-to) | 1421-1429 |
Number of pages | 9 |
Journal | EMBO Journal |
Volume | 14 |
Issue number | 7 |
DOIs | |
State | Published - 1995 |
Keywords
- Cytokines
- JAKs
- Mutants
- STATs
- Signal transduction