An immune-induced Reeler protein is involved in the Bombyx mori melanization cascade

Bao, Yan-Yuan; Xue, Jian; Wu, Wenjuan; Wang, Ying; Lv, Zu-Yao; Zhang, Chuan‐Xi

doi:10.1016/j.ibmb.2011.05.001

Cited by 39 publications

(34 citation statements)

References 30 publications

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“…M. sexta Reeler is a bacteria-induced protein with a single reeler domain following a signal peptide (Zhu et al, 2003). B. mori Reeler1 is expressed in hemocytes, fat body, and midgut in response to bacterial injection (Bao et al, 2011). RNA interference and injection of the recombinant protein affected nodule formation and proPO activation.…”

Section: Resultsmentioning

confidence: 99%

Phylogenetic analysis and expression profiling of the pattern recognition receptors: Insights into molecular recognition of invading pathogens in Manduca sexta

Zhang

Cao

et al. 2015

Insect Biochemistry and Molecular Biology

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Pattern recognition receptors (PRRs) detect microbial pathogens and trigger innate immune responses. Previous biochemical studies have elucidated the physiological functions of eleven PRRs in Manduca sexta but our understanding of the recognition process is still limited, lacking genomic perspectives. While 34 C-type lectin-domain proteins and 16 Toll-like receptors are reported in the companion papers, we present here 120 other putative PRRs identified through the genome annotation. These include 76 leucine-rich repeat (LRR) proteins, 14 peptidoglycan recognition proteins, 6 EGF/Nim-domain proteins, 5 β-1,3-glucanase-related proteins, 4 galectins, 4 fibrinogen-related proteins, 3 thioester proteins, 5 immunoglobulin-domain proteins, 2 hemocytins, and 1 Reeler. Sequence alignment and phylogenetic analysis reveal the evolution history of a diverse repertoire of proteins for pathogen recognition. While functions of insect LRR proteins are mostly unknown, their structure diversification is phenomenal: In addition to the Toll homologs, 22 LRR proteins with a signal peptide are expected to be secreted; 18 LRR proteins lacking signal peptides may be cytoplasmic; 36 LRRs with a signal peptide and a transmembrane segment may be non-Toll receptors on the surface of cells. Expression profiles of the 120 genes in 52 tissue samples reflect complex regulation in various developmental stages and physiological states, including some likely by Rel family transcription factors via κB motifs in the promoter regions. This collection of information is expected to facilitate future biochemical studies detailing their respective roles in this model insect.

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Section: Resultsmentioning

confidence: 99%

Phylogenetic analysis and expression profiling of the pattern recognition receptors: Insights into molecular recognition of invading pathogens in Manduca sexta

Zhang

Cao

et al. 2015

Insect Biochemistry and Molecular Biology

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“…Gandhe et al (Gandhe et al, 2007) reported reduction of PO activity upon Noduler knockdown but suggested further validation. The Noduler ortholog Reeler 1 was found to be necessary for PPO activation and nodulation in B. mori (Bao et al, 2011). We also performed RNAi of Hemolin and studied its effect on the PPO expression and found no obvious change in the PPO expression.…”

Section: Discussionmentioning

confidence: 96%

“…Our group previously identified an immune protein, Noduler, from the cDNA library of bacteria-challenged A. mylitta fat body and reported its upregulation upon bacterial infection (Gandhe et al, 2006;Gandhe et al, 2007). Although Noduler is implicated in melanization (Gandhe et al, 2007;Bao et al 2011), there is no information on its localization or role in nodule formation and associated signalling pathways. In the present study, we elucidated that Noduler is localized on all the hemocyte sub-types and mediates nodulation via activation of p38 signalling.…”

Section: Discussionmentioning

confidence: 99%

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Noduler an immune protein augments infection-induced cell proliferation through cross-talking with p38 MAPK

2016

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“…Dasatinib, a novel orally bioactive TKI currently used to treat patients with hematologic and solid malignancies, correlated with a combined targeting of PDGFR-β and VEGFR/c-Src signaling pathways (7)(8)(9). The Src kinases have multiple substrates that lead to diverse biological effects in cancer cells, including changes in proliferation, motility, invasion, survival and angiogenesis (10). Dasatinib suppresses tumor angiogenesis, invasion, and metastasis by inhibiting Src expression (11).…”

Section: Introductionmentioning

confidence: 99%

Enhanced antitumor activity by the combination of dasatinib and combretastatin A-4 in vitro and in vivo

Zhang

Zhou

et al. 2013

Oncology Reports

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Abstract. The present study showed that the combination of dasatinib and combretastatin A-4 (CA-4) exhibited synergistic cytotoxicity in multiple types of cancer, including ovarian, hepatocellular, lung and prostate carcinoma. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis. A clear increase in γ-H2AX expression was observed in the dasatinib + CA-4 group compared with the mono-treatment groups, indicating that dasatinib plus CA-4 may induce double-strand breaks (DSBs) in HO-8910 cells. Moreover, the increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice. Our study is the first to show that the combination of dasatinib with CA-4 could be a novel and promising therapeutic approach for the treatment of cancer. IntroductionCombretastatin A-4 (CA-4), a natural product isolated from the bark of a south african tree combretum caffrum, is a highly effective antiangiogenic agent that causes vascular shutdown, leading to tumor death (1). CA-4 phosphate (CA-4P), a water soluble pro-drug of CA-4, is rapidly dephosphorylated to the active compound CA-4 and shows reversible binding kinetics to tubulin, leading to disruption of microtubular structures (2,3). Although CA-4P is being studied in clinical trials as a vascular disrupting agent, cardiovascular toxicity and neurotoxicity are dose limiting for CA-4P (4,5). These severe side-effects currently represent the main obstacles to broad clinical application of CA-4P (2). Thus, it is important to develop new antitumor combination therapy with lower concentrations of CA-4 and more specificity for tumor endothelial cells than normal endothelial cells to avoid cardiac toxicity from endothelial damage.Tyrosine kinase inhibitors (TKIs) are rapidly being integrated into the management of a variety of malignant diseases (6). Dasatinib, a novel orally bioactive TKI currently used to treat patients with hematologic and solid malignancies, correlated with a combined targeting of PDGFR-β and VEGFR/c-Src signaling pathways (7-9). The Src kinases have multiple substrates that lead to diverse biological effects in cancer cells, including changes in proliferation, motility, invasion, survival and angiogenesis (10). Dasatinib suppresses tumor angiogenesis, invasion, and metastasis by inhibiting Src expression (11). Cardiovascular and hematologic toxicity are dose limiting for dasatinib; thus, it is necessary to develop new anticancer combination therapy with lower concentrations of dasatinib to avoid these major side-effects (12). Dasatinib has shown synergistic anticancer activity in combination with chemotherapeutic agents including paclitaxel, ixabepil...

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An immune-induced Reeler protein is involved in the Bombyx mori melanization cascade

Cited by 39 publications

References 30 publications

Phylogenetic analysis and expression profiling of the pattern recognition receptors: Insights into molecular recognition of invading pathogens in Manduca sexta

Phylogenetic analysis and expression profiling of the pattern recognition receptors: Insights into molecular recognition of invading pathogens in Manduca sexta

Noduler an immune protein augments infection-induced cell proliferation through cross-talking with p38 MAPK

Enhanced antitumor activity by the combination of dasatinib and combretastatin A-4 in vitro and in vivo

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