The torso receptor protein-tyrosine kinase signaling pathway: An endless story

Abstract

Norbert Perrimon Howard Hughes Medical Institute Department of Genetics Harvard Medical School Boston, Massachusetts 02115 One of the mechanisms by which cells respond to extracel- lular signals involves activation at the membrane of recep- tor protein-tyrosine kinases. Some of the molecules that transduce the signals generated by activated receptor pro- tein-tyrosine kinases and that ultimately activate transcrip- tion factors have been extensively characterized, and a general picture has begun to emerge. Two general conclu- sions can be drawn from studies on the control of cell growth and differentiation of mammalian cells and genetic analyses of pathways that control cell fate determination in both Caenorhabditis elegans and Drosophila melano- gaster. First, molecules involved in receptor protein- tyrosine kinase signaling have been highly conserved dur- ing evolution. Second, and perhaps more surprisingly, it appears that all receptor protein-tyrosine kinases activate a common set of molecules that includes p21”, Ras- associated regulatory proteins, Raf, MAP kinase (MAPK), and Mek (MAPK or Erk kinase). Here, our current under- standing of the Drosophila torso (tor) receptor protein- tyrosine kinase signaling pathway is described. The torso pathway, together with the Drosophila sevenless pathway required for photoreceptor R7 development and the C. elegans Let-23 pathway required for vulva1 development, has been used genetically to dissect a receptor protein- tyrosine kinase signaling pathway. Biological Role of the Torso Signaling Pathway Genetic and embryologic analyses of the early Drosoph- ila embryo have identified the terminal system, which is involved in cellular determination of both the tail and un- segmented head regions (Nusslein-Volhard et al., 1987). This system differs from the anterior (bicoid) and posterior