The Drosophila Ste20-related kinase misshapen is required for embryonic dorsal closure and acts through a JNK MAPK module on an evolutionarily conserved signaling pathway

Stress signaling in Drosophila

“…This activation is markedly decreased by simultaneous cotransfection of DN-Rac, suggesting that Msn may be upstream of Rac. Although Msn may lie in a signaling pathway with Rac, it does not interact directly with Rac (by two-hybrid or overlay assay), consistent with its lacking a de®ned GTPase binding domain (Su et al, 1998). Unlike typical ste20 kinases, such as PAK, which exhibit Rac and Cdc42 binding domains coupled to C terminal kinase domains, SPS-1 subfamily ste20-related kinases, for which Msn is highly related, have no GTPase binding sites and have N-terminal kinase domains (Kyriakis, 1999).…”

“…These methods have successfully converged to implicate misshapen (msn) in the regulation of DC and JNK signaling (Su et al, 1998). Msn was originally identi®ed as a target of an eye-speci®c transcription factor and msn mutant clones in the eye lead to abnormal photoreceptor morphology (Treisman et al, 1997).…”

“…Msn was originally identi®ed as a target of an eye-speci®c transcription factor and msn mutant clones in the eye lead to abnormal photoreceptor morphology (Treisman et al, 1997). Embryos zygotically mutant for msn show a low penetrance dorsal open phenotype (Su et al, 1998). Cloning the msn gene revealed that it is a member of the growing superfamily of protein kinases related to mammalian PAK and yeast sterile 20 (ste20), a kinase required for the mating response (Herskowitz, 1995).…”

“…To address whether Msn indeed impinges on the JNK cascade in Drosophila, cellular and genetic analysis was undertaken. Both Msn and its mammalian homolog, NIK (NCK-interacting kinase), can stimulate JNK activity in transfected cells (Su et al, 1998). This activation is markedly decreased by simultaneous cotransfection of DN-Rac, suggesting that Msn may be upstream of Rac.…”

“…For example, in msn mutant embryos, there is a substantial reduction in dpp transcript accumulation in the LE (Su et al, 1998). Additionally, expression of an activated form of c-Jun or an activated Tkv receptor can partially rescue msn mutant embryos.…”