A Temperature-Sensitive MEK Mutation Demonstrates the Conservation of the Signaling Pathways Activated by Receptor Tyrosine Kinases

Hsu, Jui-ChouPerrimon, Norbert2021-10-061994-09-15Hsu, Jui-Chou, Norbert Perrimon. "A Temperature-Sensitive MEK Mutation Demonstrates the Conservation of the Signaling Pathways Activated by Receptor Tyrosine Kinases." Genes & Development 8, no. 18 (1994): 2176-2187. DOI: 10.1101/gad.8.18.21760890-93691549-5477https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369706MEK, a dual specificity threonine/tyrosine kinase, has been postulated to be a convergent point for signaling from receptor protein tyrosine kinases (RTKs) and G-protein-coupled receptors. In contrast to yeast and mammalian cells where several MEKs have been isolated, only one Drosophila MEK (D-Mek) has been characterized to date. Previous studies have shown that D-Mek acts in the Torso RTK signaling pathway. To demonstrate that D-Mek also operates downstream of other RTKs, we generated a temperature-sensitive allele of D-mek (D-mekts) by site-directed mutagenesis based on the amino acid change of a yeast cdc2ts mutation. Using D-mekts, we show that in addition to its role in Torso signaling, D-Mek operates in the Sevenless and in the Drosophila epidermal growth factor RTK pathways. Because loss-of-function mutations in D-mek and the upstream receptors give rise to similar phenotypes, it suggests that D-mek is the only MEK activated by Drosophila RTKs. In addition, we demonstrate that different RTK pathways respond differently to alteration in D-Mek activity.en-USResearch Subject Categories::NATURAL SCIENCES::Biology::Cell and molecular biology::GeneticsA Temperature-Sensitive MEK Mutation Demonstrates the Conservation of the Signaling Pathways Activated by Receptor Tyrosine KinasesJournal Article2021-10-0610.1101/gad.8.18.2176