1. Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila
- Author
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Norbert Perrimon, Willis X. Li, Hervé Agaisse, Bernard Mathey-Prevot, Unité de recherche Génétique Microbienne (UGM), and Institut National de la Recherche Agronomique (INRA)
- Subjects
Embryo, Nonmammalian ,MAP Kinase Signaling System ,[SDV]Life Sciences [q-bio] ,Receptor Protein-Tyrosine Kinases ,Polymerase Chain Reaction ,Article ,stat ,Receptor tyrosine kinase ,Consensus Sequence ,Animals ,Drosophila Proteins ,Protein inhibitor of activated STAT ,SOCS3 ,Molecular Biology ,STAT4 ,STAT6 ,gène torso ,Base Sequence ,biology ,fungi ,Gene Expression Regulation, Developmental ,JAK-STAT signaling pathway ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,STAT Transcription Factors ,INSECTE ,Drosophila melanogaster ,Mutation ,Trans-Activators ,biology.protein ,Plasmids ,Developmental Biology - Abstract
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 (TorGOF) 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.
- Published
- 2002