A GAIN-OF-FUNCTION MUTATION IN DROSOPHILA MAP KINASE ACTIVATES MULTIPLE RECEPTOR TYROSINE KINASE SIGNALING PATHWAYS

In the Drosophila eye, activation of the sevenless (sev) receptor tyrosine kinase is required for the specification of the R7 photoreceptor cell fate. In a genetic screen for mutations that result in the activation of the sev signaling pathway in the absence of the inducing signal, we identified a gain-of-function mutation in rolled (rl(Sevenmaker) [rl(Sem)]), which encodes a homolog of mitogen-activated protein (MAP) kinase. In addition to the sev pathway, this mutation activates the pathways controlled by torso and the epidermal growth factor receptor homolog. The rl(Sem) mutation results in the substitution of a single conserved amino acid in the kinase domain. Activation of MAP kinase by the rl(Sem) mutation is both necessary and sufficient to activate multiple signaling pathways controlled by receptor tyrosine kinases.