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TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development
Y Takatsu1, M Nakamura, M Stapleton
1Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Abstract:
Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK superfamily and has been characterized as a component of the TGF-beta/bone morphogenetic protein signaling pathway. TAK1 function has been extensively studied in cultured cells, but its in vivo function is not fully understood. In this study, we isolated a Drosophila homolog of TAK1 (dTAK1) which contains an extensively conserved NH(2)-terminal kinase domain and a partially conserved COOH-terminal domain. To learn about possible endogenous roles of TAK1 during animal development, we generated transgenic flies which express dTAK1 or the mouse TAK1 (mTAK1) gene in the fly visual system. Ectopic activation of TAK1 signaling leads to a small eye phenotype, and genetic analysis reveals that this phenotype is a result of ectopically induced apoptosis. Genetic and biochemical analyses also indicate that the c-Jun amino-terminal kinase (JNK) signaling pathway is specifically activated by TAK1 signaling. Expression of a dominant negative form of dTAK during embryonic development resulted in various embryonic cuticle defects including dorsal open phenotypes. Our results strongly suggest that in Drosophila melanogaster, TAK1 functions as a MAPKKK in the JNK signaling pathway and participates in such diverse roles as control of cell shape and regulation of apoptosis.
Insights
Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is crucial for animal development. This study reveals TAK1
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is a MAPKKK superfamily member involved in TGF-beta/bone morphogenetic protein signaling.
- While TAK1 function is well-studied in cell culture, its in vivo roles during animal development remain largely unknown.
Purpose of the Study:
- To investigate the endogenous roles of TAK1 in animal development by studying its Drosophila homolog, dTAK1.
- To elucidate the signaling pathways and developmental processes regulated by TAK1 in vivo.
Main Methods:
- Isolation of a Drosophila homolog of TAK1 (dTAK1).
- Generation of transgenic flies expressing dTAK1 or mouse TAK1 (mTAK1) in the visual system.
- Genetic and biochemical analyses to determine pathway activation and developmental effects.
Main Results:
- Ectopic activation of TAK1 signaling in flies induced a small eye phenotype, attributed to apoptosis.
- TAK1 signaling specifically activates the c-Jun amino-terminal kinase (JNK) pathway.
- Expression of dominant-negative dTAK caused embryonic cuticle defects, including dorsal open phenotypes.
Conclusions:
- In Drosophila melanogaster, TAK1 functions as a MAPKKK within the JNK signaling pathway.
- TAK1 plays significant roles in regulating apoptosis and controlling cell shape during development.