Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila.
Malignant transformation frequently involves aberrant signaling from receptor tyrosine kinases (RTKs). These receptors commonly activate Ras/Raf/MEK/MAPK signaling but when overactivated can also induce the JAK/STAT pathway, originally identified as the signaling cascade downstream of cytokine receptors. Inappropriate activation of STAT has been found in many human cancers. However, the contribution of the JAK/STAT pathway in RTK signaling remains unclear. We have investigated the requirement of the JAK/STAT pathway for signaling by wild-type and mutant forms of the RTK Torso (Tor) using a genetic approach in Drosophila. Our results indicate that the JAK/STAT pathway plays little or no role in signaling by wild-type Tor. In contrast, we find that STAT, encoded by marelle (mrl; DStat92E), is essential for the gain-of-function mutant Tor (Tor(GOF)) to activate ectopic gene expression. Our findings indicate that the Ras/Raf/MEK/MAPK signaling pathway is sufficient to mediate the normal functions of wild-type RTK, whereas the effects of gain-of-function mutant RTK additionally require STAT activation.
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. willis_li@URMC.Rochester.edu
Willis X
WX
Li
Herve
H
Agaisse
Bernard
B
Mathey-Prevot
Norbert
N
Perrimon
D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System / Q000235:genetics*; D009154:Mutation; D010957:Plasmids; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D050791:STAT Transcription Factors; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; D015534:Trans-Activators; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila