High impact information on tor

• Electron microscopy studies of hrs mutant larvae reveal an impairment in endosome membrane invagination and formation of multivesicular bodies (MVBs). hrs mutant animals fail to degrade active epidermal growth factor (EGF) and Torso TKRs, leading to enhanced signaling and altered embryonic patterning [1].
• We show that it also interacts genetically with the receptor tyrosine kinases Torso and Sevenless, and it was first discovered through its effect on FGF receptor signaling [2].
• By using a recently developed technique of germline mosaics, we find that D-Raf can be activated by torso in the complete absence of Ras1 [3].
• The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway [3].
• In addition to the sev pathway, this mutation activates the pathways controlled by torso and the epidermal growth factor receptor homology [4].

Biological context of tor

• Finally, addition of a heterologous transcriptional activation domain to bcd renders the protein insensitive to tor-mediated repression [5].
• Evidence is presented that the tor pathway selectively masks the ability of dl to repress gene expression but has only a slight effect on activation [6].
• We have identified other products in this pathway by carrying out a mutagenesis screen for dominant suppressors of a tor gain-of-function allele [7].
• Analysis of the phenotypes generated by this hybrid gene and its interactions with mutations in other genes in the pathway has enabled us to further dissect the mechanism of tor receptor activation and to define more precisely the role of the different genes acting in this process [8].
• Down-regulation of the Drosophila morphogen bicoid by the torso receptor-mediated signal transduction cascade [5].

Anatomical context of tor

• Constitutive activation of the tor pathway causes severe embryonic defects, including disruptions in gastrulation and mesoderm differentiation, as a result of misregulation of dl target genes [6].
• One of them, torso (tor), has gain-of-function alleles which have an opposite phenotype to the lack-of-function (tor-) alleles: the segmented regions of the larval body, thorax and abdomen, are missing, whereas the acron is not affected and the telson is enlarged [9].
• Trunk (Trk), the proposed ligand for Tor, is secreted as an inactive precursor into the perivitelline fluid that lies between the embryonic membrane and the vitelline membrane (VM), the inner layer of the eggshell [10].
• Local activation of tor could be achieved if the ligand were expressed by a subpopulation of the follicle cells that surround the developing oocyte [11].
• In this study, we demonstrate that Torso has intrinsic tyrosine kinase activity and show that it is transiently tyrosine phosphorylated (activated) at syncytial blastoderm stages [12].

Associations of tor with chemical compounds

• The D-raf gene product, which is required for Torso function, is identified as a 90-kDa protein with intrinsic serine/threonine kinase activity [12].
• Drosophila terminal structure development is regulated by the compensatory activities of positive and negative phosphotyrosine signaling sites on the Torso RTK [13].
• At the poles of the Drosophila embryo, cell fate is established by a pathway that begins with the activation of a membrane-associated tyrosine kinase (the torso gene product); this then leads to activation of a serine/threonine kinase (Drosophila Raf-1) [14].
• The alanine-rich domain, previously described as an activation domain in vitro, has a repressive activity that is independent of Torso [15].
• The alanine-rich domain contributes to this process indirectly by reducing the global activity of the protein and in particular the activity of the glutamine-rich domain that might otherwise prevent downregulation by Torso [15].

Physical interactions of tor

• These results suggest that the tsl protein is the ligand that binds to the torso receptor [16].
• These findings suggest that mutant forms of D-raf may deplete the embryo of a positive activator and/or form inactive protein complexes that affect rescue of the Tor pathway [17].

Enzymatic interactions of tor

• Torso contains a split tyrosine kinase domain and belongs to the type III subgroup of the RTK superfamily that also includes the platelet-derived growth factor receptors, stem cell or steel factor receptor c-Kit proto-oncoprotein, colony-stimulating factor-1 receptor, and vascular endothelial growth factor receptor [18].

Regulatory relationships of tor

• Torso signalling regulates terminal patterning in Drosophila by antagonising Groucho-mediated repression [19].
• We propose that phosphorylation resulting from the activity of the tor signal transduction cascade down-regulates transcriptional activation by the bcd morphogen [5].
• In addition, we show that a mutation in Tec29A partially suppresses a gain-of-function mutation in tor [20].
• Extending the current model, we show that activation of the Torso pathway can trigger tailless expression without eliminating Capicua [21].
• Proteolytic cleavage of the Trunk precursor can activate Torso-dependent signaling, but the existence of cleaved Trunk has not yet been demonstrated in vivo for Drosophila [22].

Other interactions of tor

• Repression does not require either tailless or huckebein, which were previously thought to constitute the sole zygotic output of the tor signaling system [5].
• Ectopic expression of tsl produced embryos with a phenotype similar to that resulting from constitutively active Tor alleles [23].
• Phosphorylation of bicoid on MAP-kinase sites: contribution to its interaction with the torso pathway [24].
• We show that torso signalling permits terminal gap gene expression by antagonising Gro-mediated repression [19].
• Intracellular kinases that are thought to function downstream of tor, such as D-raf and the rolled MAP kinase, mediate this selective block in repression [6].

Analytical, diagnostic and therapeutic context of tor

• Dissection of the Torso signal transduction pathway in Drosophila [25].
• In addition to these molecules we have characterized the putative protein tyrosine phosphatase Corkscrew as a positive transducer downstream of Torso [25].
• Similarly, transplantation of anterior and lateral wildtype cytoplasm into the anterior of tor embryos rescued anterior terminal (acron) structures, whereas posterior cytoplasm did not [26].

References