<i>mom</i> identifies a receptor for the <i>Drosophila</i> JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family

Chen, Huawei; Chen, Xiu; Oh, Su-Wan; Marinissen, Maria Julia; Gutkind, J. Silvio; Hou, Steven X.

doi:10.1101/gad.955202

Cited by 152 publications

(147 citation statements)

References 49 publications

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“…By contrast, domeless (Figure 3d), hopscotch ( Figure 3e) and stat92E (Figure 3f) mRNA's are all expressed essentially uniformly throughout third instar wing discs and explain why ectopic Upd expression is sufficient to misactivate the pathway (see below). Interestingly, the levels of STAT92E protein present in wing disc are not entirely uniform but are present at higher levels in the future notum and in central regions in which upd is expressed (Figure 3g arrow heads), a finding that is consistent with the previously described stabilization of STAT92E in actively signalling cells (Johansen et al, 2003;Chen et al, 2002;Read et al, 2004).…”

Section: Noncanonical Stat92e Activationsupporting

confidence: 78%

“…Given this unexpected result, we set out to obtain additional confirmation of this effect. As described above, STAT92E protein appears to be stabilized in response to pathway activation (Figure 3g; Chen et al, 2002;Johansen et al, 2003;Read et al, 2004 (Figure 3g), the loss of Hop activity within mutant clones located away from regions of endogenous upd expression had no influence on the levels of STAT92E protein detected (Figure 4a-c). These results suggest that STAT92E does not require Hop to mediate its antiproliferative function or its activity-related stability in late stage wing discs.…”

Section: Noncanonical Stat92e Activationmentioning

confidence: 90%

“…In flies an extracellular ligand Unpaired (Upd: Harrison et al, 1998), a trans-membrane receptor, Domeless (Dome: Brown et al, 2001;Chen et al, 2002), a JAK tyrosine kinase called Hopscotch (Hop: Binari and Perrimon, 1994) and the STAT92E transcription factor (Hou et al, 1996;Yan et al, 1996) make up the pathway. The identification of mutations in all components, in combination with the developmental genetics of the Drosophila system have lead to the identification of multiple embryonic, larval and adult developmental processes which require the pathway (reviewed in Castelli-Gair Hombrı´a and Brown, 2002;Hou et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

2005

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The JAK/STAT signalling pathway mediates both antiproliferative responses following interferon stimulation and cellular proliferation in response to cytokines such as interleukins and growth factors. Central to these responses are the seven vertebrate STAT molecules, misregulation of which is implicated in a variety of malignancies. We have investigated the proliferative role of the single Drosophila STAT92E, part of the evolutionarily conserved JAK/STAT cascade. During second instar larval wing disc development pathway activity is both necessary and sufficient to promote proliferation of this epithelial cell type. However by later stages, endogenous STAT92E is stimulated by a noncannonical mechanism to exert pronounced antiproliferative effects. Ectopic canonical activation is sufficient to further decrease proliferation and leads to the premature arrest of cells in the G2 phase of the cell cycle. The single STAT92E present in Drosophila therefore mediates both proproliferative functions analogous to vertebrate interleukin-stimulated STAT3 and antiproliferative functions analogous to interferon-stimulated STAT1. Pro-and antiproliferative roles therefore represent ancestral activities conserved through evolution and subsequently assigned to distinct molecules.

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Section: Noncanonical Stat92e Activationsupporting

confidence: 78%

Section: Noncanonical Stat92e Activationmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

2005

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“…We show that loss of NURF resembles gain-of-function mutations in hop, and that targets of the HOP/STAT92E cascade are upregulated in nurf301 mutants. Normally, HOP activation leads to the expression and posttranslational modification of STAT92E (Chen et al 2002). We found that although nurf301 mutants activate the HOP/STAT92E pathway, the levels of the STAT92E transcription factor are unchanged in NURF mutant animals.…”

Section: Nurf and Tumorigenesismentioning

confidence: 68%

Biological functions of the ISWI chromatin remodeling complex NURF

Badenhorst

Voas²,

Rebay³

et al. 2002

Genes Dev.

209

198

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The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form.

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“…Interestingly, the CBDs and FNIII domains of GPL and Dome are 29.7% similar, suggesting that they share a common origin. Dome appears to be a unique large-size cytokine receptor present in the Drosophila genome (50,51). Dome and gpl are probably related to an ancestral receptor that gave rise to the entire family of cytokine receptors.…”

Section: Discussionmentioning

confidence: 99%

GPL, a Novel Cytokine Receptor Related to GP130 and Leukemia Inhibitory Factor Receptor

Diveu

Lelièvre

Perret

et al. 2003

Journal of Biological Chemistry

103

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We describe a novel cytokine receptor named GP130 Like receptor, or GPL, that displays similarities with the interleukin-6 and interleukin-12 family of signaling receptors. Four different isoforms diverging in their carboxyl terminus were isolated, corresponding to proteins encompassing 560, 610, 626, and 745 amino acids. Sequences included a signal peptide of 32 amino acids, followed by a cytokine binding domain containing four conserved cysteines, a WSDWS motif, and a region consisting of three fibronectin type III domain repeats. No immunoglobulin-like module was identified in the GPL sequences. The intracellular part of longer isoforms contained a proline-rich region defining a box1 motif for interaction with the Janus kinases. The Gpl gene is organized in 15 exons and is located on 5q11.2 in tandem with the gp130 gene. Both genes were only separated by 24 kilobases, with opposite transcriptional orientations. The GPL receptor displayed a 28% identity with gp130. Specific GPL transcripts were observed in tissues involved in reproduction. Transcripts were also found in blood cells and in bone marrow, revealing expression of GPL in all of the myelomonocytic lineage, from hematopoietic stem cells to activated dendritic cells. In monocytes and dendritic cells, expression of GPL was strongly up-regulated by interferon-␥, indicating a possible involvement of GPL in Th1-type immune responses. The molecular basis of cell signaling mediated by GPL was studied using chimeric receptors where external portions of ␣ or ␤ interleukin-5 receptor subunits were fused to the internal portion of GPL or of related receptors. Results indicated that association of GPL to the intracellular portions of gp130, or LIF receptor, allowed the signaling cascade.

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mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family

Cited by 152 publications

References 49 publications

Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

Biological functions of the ISWI chromatin remodeling complex NURF

GPL, a Novel Cytokine Receptor Related to GP130 and Leukemia Inhibitory Factor Receptor

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