Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|Eq, M, H, R, Ca, Xn, Ch, B||IP, WB, EA||Rb||Affinity Purified||Polyclonal Antibody|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Stable for 1 year at 2-8°C from date of receipt.|
|Reference overview||Pub Med ID|
|Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells. |
Vinicius Toledo Ribas,Bruno Souza Gonçalves,Rafael Linden,Luciana Barreto Chiarini
PloS one 7 2012
Most studies of c-Jun N-terminal Kinase (JNK) activation in retinal tissue were done in the context of neurodegeneration. In this study, we investigated the behavior of JNK during mitosis of progenitor cells in the retina of newborn rats. Retinal explants from newborn rats were kept in vitro for 3 hours and under distinct treatments. Sections of retinal explants or freshly fixed retinal tissue were used to detect JNK phosphorylation by immunohistochemistry, and were examined through both fluorescence and confocal microscopy. Mitotic cells were identified by chromatin morphology, histone-H3 phosphorylation, and location in the retinal tissue. The subcellular localization of proteins was analyzed by double staining with both a DNA marker and an antibody to each protein. Phosphorylation of JNK was also examined by western blot. The results showed that in the retina of newborn rats (P1), JNK is phosphorylated during mitosis of progenitor cells, mainly during the early stages of mitosis. JNK1 and/or JNK2 were preferentially phosphorylated in mitotic cells. Inhibition of JNK induced cell cycle arrest, specifically in mitosis. Treatment with the JNK inhibitor decreased the number of cells in anaphase, but did not alter the number of cells in either prophase/prometaphase or metaphase. Moreover, cells with aberrant chromatin morphology were found after treatment with the JNK inhibitor. The data show, for the first time, that JNK is activated in mitotic progenitor cells of developing retinal tissue, suggesting a new role of JNK in the control of progenitor cell proliferation in the retina.
|CD22 regulates adaptive and innate immune responses of B cells. |
Norihito Kawasaki,Christoph Rademacher,James C Paulson
Journal of innate immunity 3 2011
B cells sense microenvironments through the B cell receptor (BCR) and Toll-like receptors (TLRs). While signals from BCR and TLRs synergize to distinguish self from nonself, inappropriate regulation can result in development of autoimmune disease. Here we show that CD22, an inhibitory co-receptor of BCR, also negatively regulates TLR signaling in B cells. CD22-deficient (Cd22(-/-)) B cells exhibit hyperactivation in response to ligands of TLRs 3, 4 and 9. Evidence suggests that this results from impaired induction of suppressors of cytokine signaling 1 and 3, well-known suppressors of TLR signaling. Antibody-mediated sequestration of CD22 on wild-type (WT) B cells augments proliferation by TLR ligands. Conversely, expression of CD22 in a Cd22(-/-) B cell line blunts responses to TLR ligands. We also show that lipopolysaccharide-induced transcription by nuclear factor-ÎºB is inhibited by ectopic expression of CD22 in a TLR4 reporter cell line. Taken together, these results suggest that negative regulation of TLR signaling is an intrinsic property of CD22. Since TLRs and BCR activate B cells through different signaling pathways, and are differentially localized in B cells, CD22 exhibits a broader regulation of receptors that mediate adaptive and innate immune responses of B cells than previously recognized.
|Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion. |
Cheng-Hsun Ho, Chi-Long Chen, Wing-Yin Li, Chi-Ju Chen, Cheng-Hsun Ho, Chi-Long Chen, Wing-Yin Li, Chi-Ju Chen
Carcinogenesis 30 1443-51 2009
Decoy receptor 3 (DcR3), a member of tumor necrosis factor receptor superfamily, has been implicated in tumorigenesis through its abilities to modulate immune responses and induce angiogenesis. Epstein-Barr virus (EBV), a ubiquitous gamma-herpesvirus, is associated with malignancies including nasopharyngeal carcinoma (NPC). Previous studies show that DcR3 is overexpressed in EBV-positive lymphomas and Rta, an EBV transcription activator, can upregulate DcR3 in Burkitt lymphoma cell lines. However, DcR3 expression has not been demonstrated in EBV-associated NPC nor have there been any EBV latent genes linked to DcR3 upregulation. Here, we showed DcR3 was overexpressed in NPC. Higher DcR3 expression score and DcR3-positive rate were found in metastatic NPC than in primary NPC tissues, suggesting DcR3 may enhance cell metastatic potential. This hypothesis is supported by our observation that NPC HONE-1 cells overexpressing DcR3 exhibited significant higher migration and invasion abilities in vitro. We found besides Rta, EBV latent membrane protein (LMP) 1 can upregulate DcR3 via nuclear factor-kappaB and phosphatidylinositol 3-kinase-signaling events. Approximate 75% of LMP1-positive NPC tissues overexpressed DcR3, suggesting LMP1 may enhance DcR3 expression in vivo. Data herein suggested that increasing DcR3 expression by LMP1 not only helps EBV-associated cancer cells gain survival advantage by preventing host immune detection but also increases the chance of cancer metastasis by enhancing cell migration and invasion. All these DcR3-mediated events facilitate normal cells to gain cancer hallmarks.
|Subcellular receptor redistribution and enhanced microspike formation by a Ret receptor preferentially recruiting Dok. |
Anna Stenqvist, T Kalle Lundgren, Matthew J Smith, Ola Hermanson, Gonçalo Castelo-Branco, Tony Pawson, Patrik Ernfors
Neuroscience letters 435 11-6 2008
Ret is a receptor tyrosine kinase for the GDNF family of ligands and plays important roles during nervous system development for cell proliferation, cell migration and neurite growth. Signaling initiated from intracellular tyrosine 1062, by recruitment of several different phosphotyrosine binding (PTB) proteins (i.e. Shc, Frs2 and Dok), is important for these biological effects. By a single amino acid substitution in the PTB domain binding sequence of Ret, we have rewired the receptor such that it preferentially recruits Dok (Ret(Dok+)) with little or no remaining interactions with Shc and Frs2. Ret(Dok+) displays a sustained MAP kinase activation and a loss of Akt signaling compared to Ret(WT). We show that early events after ligand stimulation of Ret(Dok+) include massive formation of fine microspikes that are believed to be priming structures for neurite growth from the cell soma. The Ret(Dok+) receptors relocated in the membrane compartment into focal clusters at the tip of the microspikes, which was associated with Cdc42 activation. These results suggest that engagement of different adaptor proteins by Ret results in very different downstream signaling and functions within neurons and that Dok recruitment leads to a rapid receptor relocation and formation of microspikes.
|WNT pathways in the neonatal ovine uterus: potential specification of endometrial gland morphogenesis by SFRP2. |
Kanako Hayashi, Thomas E Spencer
Biology of reproduction 74 721-33 2006
Endometrial glands are critical for uterine function and develop between birth (Postnatal Day [P] 0) and P56 in the neonatal ewe. Endometrial gland morphogenesis or adenogenesis involves the site-specific budding differentiation of the glandular epithelium from the luminal epithelium followed by their coiling/branching development within the stroma of the intercaruncular areas of the endometrium. To determine whether WNT signaling regulates endometrial adenogenesis, the WNT signaling system was studied in the neonatal ovine uterus. WNT5A, WNT7A, and WNT11 were expressed in the uterine epithelia, whereas WNT2B was in the stroma. The WNT receptors FZD2 and FZD6 and coreceptor LRP6 were detected in all uterine cells, and FZD6 was particularly abundant in the endometrial epithelia. Secreted FZD-related protein-2 (SFRP2), a WNT antagonist, was not detected in the P0 uterus, but was abundant in the aglandular caruncular areas of the endometrium between P7 and P56. Exposure of ewes to estrogens during critical developmental periods inhibits or retards endometrial adenogenesis. Estrogen-induced disruption of endometrial adenogenesis was associated with reduction or ablation of WNT2B, WNT7A, and WNT11, and with an increase in WNT2 and SFRP2 mRNA, depending on exposure period. Collectively, results implicate the canonical and noncanonical WNT pathways in regulation of postnatal ovine uterine development and endometrial adenogenesis. Expression of SFRP2 in aglandular caruncular areas may inhibit the WNT signaling pathway, thereby concentrating WNT signaling and restricting endometrial adenogenesis in the intercaruncular areas of the uterus. Further, estrogen-induced inhibition of adenogenesis may be mediated by a reduction in WNT signaling caused by aberrant induction of SFRP2 and loss of several critical WNTs.