Dominant mutations of Drosophila MAP kinase kinase and their activities in Drosophila and yeast MAP kinase cascades

• Published in: Genetics (Austin) 1997-05, Vol.146 (1), p.263-273
• Main Authors: Lim, Y.M. (Nagoya University, Nagoya, Japan.), Tsuda, L, Inoue, Y.H, Irie, K, Adachi-Yamada, T, Hata, M, Nishi, Y, Matsumoto, K, Nishida, Y
• Format: Article
• Language: English
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; ALLELES; Amino Acid Sequence; AMINO ACID SEQUENCES; ANIMAL CUTICLE; Animals; CHEMICAL COMPOSITION; COMPLEMENTATION; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; COMPOUND EYES; CUTICULA ANIMAL; CUTICULE ANIMALE; DESARROLLO EMBRIONARIO; DEVELOPPEMENT EMBRYONNAIRE; DOMINANCE; DOMINANT SUPPRESSORS; Drosophila; Drosophila - genetics; DROSOPHILA MELANOGASTER; Drosophila Proteins; DSOR1 ALLELES; EMBRYONIC DEVELOPMENT; ENZYMIC ACTIVITY; EXPRESION GENICA; EXPRESSION DES GENES; Eye - enzymology; Eye - ultrastructure; EYES; FENOTIPOS; GENE; GENE EXPRESSION; GENE TRANSFER; GENES; Genes, Dominant; GENETIC TRANSFORMATION; GENETICA; GENETICS; GENETIQUE; INHIBITOR GENES; Insects; Investigations; Male; Microscopy, Electron; MITOGEN ACTIVATED PROTEIN KINASE KINASE; Molecular Sequence Data; MUTACION; MUTATION; NUCLEOTIDE SEQUENCE; OEIL; OJOS; PHENOTYPE; PHENOTYPES; PROTEIN KINASE; Protein Kinases - chemistry; Protein Kinases - genetics; Protein Kinases - metabolism; PROTEINA QUINASA; PROTEINE KINASE; Proteins; RECEPTOR TYROSINE KINASE; RECEPTORS; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - genetics; SECUENCIA NUCLEOTIDICA; Sequence Homology, Amino Acid; SEQUENCE NUCLEOTIDIQUE; TRANSFERENCIA DE GENES; TRANSFERT DE GENE; TRANSFORMACION GENETICA; TRANSFORMATION GENETIQUE
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1093/genetics/146.1.263

Eight alleles of Dsor1 encoding a Drosophila homologue of mitogen-activated protein (MAP) kinase kinase were obtained as dominant suppressors of the MAP kinase kinase kinase D raf. These Dsor1 alleles themselves showed no obvious phenotypic consequences nor any effect on the viability of the flies, although they were highly sensitive to upstream signals and strongly interacted with gain-of-function mutations of upstream factors. They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER). Furthermore, the Dsor1 alleles showed no significant interaction with gain-of-function mutations of DER. The observed difference in activity of the Dsor1 alleles among the RTK pathways suggests Dsor1 is one of the components of the pathway that regulates signal specificity. Expression of Dsor1 in budding yeast demonstrated that Dsor1 can activate yeast MAP kinase homologues if a proper activator of Dsor1 is coexpressed. Nucleotide sequencing of the Dsor1 mutant genes revealed that most of the mutations are associated with amino acid changes at highly conserved residues in the kinase domain. The results suggest that they function as suppressors due to increased reactivity to upstream factors.