Disease relevance of Stat92E

• In contrast, expression of a kinase-inactive form of Dsrc caused distinct nervous system abnormalities in embryos and decreased the numbers of photoreceptor cells in the adult eye ommatidia [1].
• White spot syndrome virus annexes a shrimp STAT to enhance expression of the immediate-early gene ie1 [2].

High impact information on Stat92E

• Two D-STAT-binding sites were identified within the eve stripe 3 enhancer region [3].
• We show that a reduction in the amount of marelle gene activity suppresses the phenotype associated with a gain-of-function mutation in hopscotch and enhances the phenotype associated with a weak hopscotch mutation [4].
• Of the 29 positive regulators, 13 are required for the tyrosine phosphorylation of STAT92E [5].
• The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development [6].
• By increasing the DeltaNSTAT92E-to-STAT92E ratio in overexpression and RNAi experiments, we observe phenotypes compatible with suppression of wild-type STAT92E activity [7].

Biological context of Stat92E

• An analysis of mosaic clones, using an apparent null stat92E allele, indicates that Stat92E is required in the polar/stalk follicle cell lineage [8].
• Here we identify Drosophila Stat92E (signal transducer and activator of transcription) in a screen for gain-of-function suppressors of the slbo mutant phenotype [9].
• However, Stat92E mutant cells still express normal levels of Slbo protein, thus Stat92E must regulate other targets critical for border cell migration [9].
• These constructs differ by the number of Stat92E binding sites and the stability of GFP [10].
• Altogether, our data indicate that Dome is an essential receptor molecule for Upd and JAK/STAT signaling during oogenesis [11].

Anatomical context of Stat92E

• Genetic analysis of contributions of dorsal group and JAK-Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila [12].
• One of these mutants, statHJ, mapped to the same chromosomal region (92E) as does D-Stat, had an incompletely penetrant pair rule phenotype, and exhibited aberrant expression of the pair rule gene even skipped (eve) at the cellular blastoderm stage [3].
• In Drosophila, a conserved JAK/STAT signaling pathway controls segmentation in embryos, as well as blood cell development and other processes in larvae and adults [11].
• We demonstrate that mutants for domeless or any other known component of the canonical JAK/STAT signaling pathway display a failure of coordinated cell movement during the development of the proventriculus, a multiply folded organ which is formed by stereotyped cell rearrangements in the posterior foregut [13].
• Taken together with the appearance of STAT92E in a gradient in the hindgut epithelium, these results support a model in which an anteroposterior gradient of ligand results in a gradient of activated STAT [14].

Associations of Stat92E with chemical compounds

• By band mobility shift assay, we detected a factor binding to the D-STAT-recognition sequence in extracts of cultured Drosophila cells treated with vanadate peroxide [15].
• Expression of both wild type Dsrc and a C-terminally truncated mutant at high levels during embryonic development induced extensive tyrosine phosphorylation of cellular proteins and caused considerable lethality, correlating with a block to germ-band retraction [1].
• Stimulation with lipopolysaccharide resulted in an increase of tyrosine phosphorylation and DNA binding activity of AaSTAT and CtSTAT as well as an increase of luciferase activity of a reporter gene containing Drosophila STAT binding motif in mosquito C6/36 cells [16].

Physical interactions of Stat92E

• The JAK/STAT signaling pathway plays important roles in vertebrate development and the regulation of complex cellular processes [17].
• We also found that the D-STAT-binding site is required for injury-induced activation of the D-raf gene promoter [15].
• In addition, mutations in the Jak/STAT pathway interact genetically with the Notch pathway by suppressing Notch mediated overgrowth [18].

Regulatory relationships of Stat92E

• Conversely, wg is autonomously repressed in cells with hyperactivated Stat92E [19].
• Here we propose that D-STAT can participate in regulation of the mitogen-activated protein kinase cascade through D-raf gene activation [15].
• Both the lethality and the eye roughening caused by activated Dsrc were partially suppressed by mutations in the Drosophila Ras1 gene [1].
• SOCS36E is expressed in an essentially identical pattern to the Drosophila JAK/STAT pathway ligand unpaired (Upd) [20].
• Recently we have shown that in Drosophila the receptor tyrosine kinase Torso activates both STAT and Ras during the early phase of PGC development [21].

Other interactions of Stat92E

• In addition, these reporters accurately reflect JAK/STAT pathway activity at larval stages, as their expression pattern overlaps that of the activating ligand unpaired in imaginal discs [10].
• Cooperation of JAK/STAT and Notch signaling in the Drosophila foregut [13].
• Larvae carrying loss-of-function mutations in dorsal group genes (including Toll and tube) have reduced hemocyte concentrations, whereas larvae deficient in Hopscotch-Stat92E signaling do not [12].
• Taken together, our study is the first to demonstrate a role for the JAK/STAT pathway in regional specification by acting antagonistically to wg [19].
• We show that upd2 is expressed in a pattern essentially identical to that of upd and demonstrate that the proteins encoded by this region activate JAK/STAT pathway signalling [22].

Analytical, diagnostic and therapeutic context of Stat92E

• Mosaic analysis of both JAK pathway transducers, hopscotch and Stat92E, reveals that JAK signaling is specifically required in the somatic follicle cells [23].
• Stat92E RNA expression is strongest in the differentiating follicle cells in the germarium, as determined by in situ hybridization [8].

References