Disease relevance of hop

• Although the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is part of the antiviral response in arthropods such as Drosophila, here we show that white spot syndrome virus (WSSV) uses a shrimp STAT as a transcription factor to enhance viral gene expression in host cells [1].
• The Drosophila Tumorous-lethal (Tum-l) mutation acts as an activated oncogene, causing hematopoietic neoplasms, overproliferation, and premature differentiation [2].
• Suppression of sterility by Wolbachia discriminates markedly among similar germline-specific Sxl alleles, and is not observed for mutations in other genes that produce similar 'tumorous ovary' phenotypes, including one that blocks Sxl germline expression [3].
• A dominant gain-of-function allele, Tumorous-lethal (hopTum-l), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs [4].
• The structure, expression and possible function of the following four tumor suppressor genes are discussed: tumorous imaginal disc, lethal (3) malignant brain tumor, lethal (3) malignant blood neoplasm-1 and benign (2) gonial cell neoplasm [5].

High impact information on hop

• JAK/STAT signaling effects have been attributed largely to direct transcriptional regulation by STAT of specific target genes that promote tumor cell proliferation or survival [6].
• JAK signaling globally counteracts heterochromatic gene silencing [6].
• 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 [7].
• Drosophila awdK-pn, a homologue of the metastasis suppressor gene nm23, suppresses the Tum-1 haematopoietic oncogene [8].
• The hub specifically expresses Unpaired, a ligand activating the JAK-STAT (Janus kinase-signal transducer and activator of transcription) signaling cascade [9].

Biological context of hop

• We have identified a putative Drosophila STAT protein named Marelle that exhibits mutant phenotypes identical to mutations in the Hopscotch/JAK kinase [7].
• The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development [10].
• Furthermore, we show that the JAK/STAT pathway regulates a small enhancer in the wg 3' cis genomic region [11].
• The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance [12].
• Phenotypic analyses of JAK and STAT mutants implicate this pathway in a number of developmental decisions, in particular the regulation of pair-rule genes and fly hematopoiesis [13].

Anatomical context of hop

• Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium [14].
• STAT92E-GFP fluorescence is increased in response to ectopic upd in the larval eye disc and mis-expression of the JAK kinase hopscotch in the adult fat body [15].
• Upd is a secreted protein, associated with the extracellular matrix, that activates the JAK pathway [16].
• By contrast, constitutively active hopscotch and hemipterous give massive activation of lamellocyte formation with little or no increase in total hemocyte numbers [17].
• 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 [18].

Associations of hop with chemical compounds

• We present a model in which the Hop tyrosine kinase is involved in the control of pair-rule gene transcription in a stripe-specific manner [19].

Physical interactions of hop

• The JAK/STAT signaling pathway plays important roles in vertebrate development and the regulation of complex cellular processes [20].
• The Dorothy enhancer has Tinman binding sites and drives hopscotch-induced tumor formation [21].

Other interactions of hop

• Our results demonstrate the existence of an invertebrate JAK/STAT system [7].
• These data show that mom functions as a receptor of the Drosophila JAK/STAT signal transduction pathway [10].
• The difference in effect between localized expression of ligand (Unpaired) and dominant active JAK (Hopscotch) demonstrates that the ligand plays a cell non-autonomous role in hindgut cell rearrangement [14].
• In addition, an activated form of Hop results in increased levels of Cactus and Dorsal proteins, modifying the Dorsal/Cactus ratio and consequently DV patterning [22].
• Here, we demonstrate that Hop requires the activity of the Raf pathway to promote the activation response of larval plasmatocytes, and provide evidence to suggest that the Hop and D-Raf proteins physically interact [23].

Analytical, diagnostic and therapeutic context of hop

• Mosaic analysis of both JAK pathway transducers, hopscotch and Stat92E, reveals that JAK signaling is specifically required in the somatic follicle cells [24].
• Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes [25].
• Finally, overexpression of either hop or hopTum-l in Drosophila cell culture results in tyrosine phosphorylation of Hop protein [4].

References