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PMID: 12183376 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila.

Development (Cambridge, England) ·Vol. 129 ·No. 18 ·2002-09-00 ·Pages 4241-8

Li WX, Agaisse H, Mathey-Prevot B, Perrimon N

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 (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.

MeSH Terms
Animals Base Sequence Consensus Sequence DNA-Binding Proteins/genetics,metabolism Drosophila Proteins/genetics Drosophila melanogaster/embryology,genetics Embryo, Nonmammalian/physiology Gene Expression Regulation, Developmental MAP Kinase Signaling System/genetics Mutation Plasmids Polymerase Chain Reaction Receptor Protein-Tyrosine Kinases/genetics,metabolism STAT Transcription Factors Trans-Activators/genetics,metabolism
Chemicals
DNA-Binding Proteins Drosophila Proteins STAT Transcription Factors Stat92E protein, Drosophila Trans-Activators Receptor Protein-Tyrosine Kinases tor protein, Drosophila
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Li Willis X
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. [email protected]
Agaisse Herve
Mathey-Prevot Bernard
Perrimon Norbert
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
Email
[email protected]
Published
2002-09-00
Pages
4241-8
Language
English
Region
England
NLM ID
8701744
PMCID
PMC3090254
Subset
IM
Grants
NIGMS NIH HHS · R01 GM065774 · United States
NIGMS NIH HHS · R01 GM065774-01 · United States
NIGMS NIH HHS · R01 GM65774-01 · United States
NHLBI NIH HHS · R01 HL62434 · United States
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PubMed source PMC Full Text View journal details
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