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Fused


AUTHORS

Ascano Manuel , Robbins David J , . UCSD-Nature Molecule Pages. 2006 3 17; ().

ABSTRACT

Drosophila that have mutations in the gene Fused (Fu) die during embryonic development, exhibiting a classic segment-polarity phenotype similar to genes involved in the Wingless and Hedgehog (Hh) signal transduction pathways. Because Fu is a maternally contributed gene, Fu mutants are able to escape embryonic lethality to reach adulthood. These adult Fu mutant flies develop a fusion between longitudinal veins 3 and 4 in their wings, the phenotype from which the gene takes its name. Fu is a member of the Hh signal transduction pathway, where it functions downstream of the Hh receptor as a putative Ser/Thr protein kinase whose activity is required for the proper activation of the Hh pathway. The Fu protein consists of two major domains: an amino-terminal Ser/Thr protein kinase domain and a carboxy-terminal regulatory domain, which bears no significant homology to any known protein. In Drosophila, Fu forms a functional interaction between its kinase and regulatory domains. In Drosophila, Fu is an integral component of a large cytoplasmic Hh signaling complex (HSC) that also contains the kinesin-related protein Costal2 (Cos2) and a zinc-finger transcription factor Cubitus interruptus (Ci). Fu can act as a positive regulator of the Hh pathway, promoting the Hh-dependent activation of Ci in a kinase-activity-dependent manner. In the absence of Hh activation, Fu also has a function in the proteolysis of Ci into a transcriptional repressor. This latter activity of Fu does not seem to require an active kinase domain. The kinase domain of Fu contains all the subdomains and specific amino acids known to be required for the proper catalytic activity of other Ser/Thr protein kinases. Furthermore, analyses of Fu mutants harboring mutations in residues critical for kinase activity results in a loss of Hh signaling.


Drosophila that have mutations in the gene Fused (Fu) die during embryonic development, exhibiting a classic segment-polarity phenotype similar to genes involved in the Wingless and Hedgehog (Hh) signal transduction pathways. Because Fu is a maternally contributed gene, Fu mutants are able to escape embryonic lethality to reach adulthood. These adult Fu mutant flies develop a fusion between longitudinal veins 3 and 4 in their wings, the phenotype from which the gene takes its name. Fu is a member of the Hh signal transduction pathway, where it functions downstream of the Hh receptor as a putative Ser/Thr protein kinase whose activity is required for the proper activation of the Hh pathway. The Fu protein consists of two major domains: an amino-terminal Ser/Thr protein kinase domain and a carboxy-terminal regulatory domain, which bears no significant homology to any known protein. In Drosophila, Fu forms a functional interaction between its kinase and regulatory domains. In Drosophila, Fu is an integral component of a large cytoplasmic Hh signaling complex (HSC) that also contains the kinesin-related protein Costal2 (Cos2) and a zinc-finger transcription factor Cubitus interruptus (Ci). Fu can act as a positive regulator of the Hh pathway, promoting the Hh-dependent activation of Ci in a kinase-activity-dependent manner. In the absence of Hh activation, Fu also has a function in the proteolysis of Ci into a transcriptional repressor. This latter activity of Fu does not seem to require an active kinase domain. The kinase domain of Fu contains all the subdomains and specific amino acids known to be required for the proper catalytic activity of other Ser/Thr protein kinases. Furthermore, analyses of Fu mutants harboring mutations in residues critical for kinase activity results in a loss of Hh signaling.


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