The Experts below are selected from a list of 59790 Experts worldwide ranked by ideXlab platform
Mingyao Liu - One of the best experts on this subject based on the ideXlab platform.
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XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis
Scientifica, 2014Co-Authors: Xiaohui Bai, Hae-ra Cho, Serisha Moodley, Mingyao LiuAbstract:Several Adaptor Proteins have previously been shown to play an important role in the promotion of tumourigenesis. XB130 (AFAP1L2) is an Adaptor Protein involved in many cellular functions, such as cell survival, cell proliferation, migration, and gene and miRNA expression. XB130's functional domains and motifs enable its interaction with a multitude of Proteins involved in several different signaling pathways. As a tyrosine kinase substrate, tyrosine phosphorylated XB130 associates with the p85α regulatory subunit of phosphoinositol-3-kinase (PI3K) and subsequently affects Akt activity and its downstream signalling. Tumourigenesis studies show that downregulation of XB130 expression by RNAi inhibits tumor growth in mouse xenograft models. Furthermore, XB130 affects tumor oncogenicity by regulating the expression of specific tumour suppressing miRNAs. The expression level and pattern of XB130 has been studied in various human tumors, such as thyroid, esophageal, and gastric cancers, as well as, soft tissue tumors. Studies show the significant effects of XB130 in tumourigenesis and suggest its potential as a diagnostic biomarker and therapeutic target for cancer treatments.
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xb130 a novel Adaptor Protein promotes thyroid tumor growth
American Journal of Pathology, 2011Co-Authors: Atsushi Shiozaki, Monika Lodyga, Xiaohui Bai, Shaf Keshavjee, Jeya Nadesalingam, Takeshi Oyaizu, Daniel A Winer, Sylvia L Asa, Mingyao LiuAbstract:Adaptor Proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel Adaptor Protein, XB130, which binds the p85α subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G 1 -S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the top-ranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators.
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Adaptor Protein xb130 is a rac controlled component of lamellipodia that regulates cell motility and invasion
Journal of Cell Science, 2010Co-Authors: Monika Lodyga, Xiaohui Bai, Andras Kapus, Mingyao LiuAbstract:XB130 is a newly described cytosolic Adaptor Protein and tyrosine kinase substrate, involved in Src- and RET/PTC-dependent signaling. Although XB130 has been cloned as a homologue of actin-filament-associated Protein (AFAP-110), its potential regulation by the actin skeleton and its putative roles in cytoskeleton regulation have not been addressed. Here, we show that XB130 (in contrast to AFAP-110) exhibited robust translocation to the cell periphery in response to various stimuli (including epidermal growth factor, wounding and expression of constitutively active Rac) that elicit lamellipodium formation. In stimulated cells, XB130 localized to the lamellipodial F-actin meshwork. Genetic and pharmacological data suggest that the key trigger for XB130 recruitment is the formation of the branched F-actin itself. Structure-function analysis revealed that both the XB130 N-terminus (167 amino acids) and C-terminus (63 amino acids) harbor crucial regions for its translocation to lamellipodia, whereas the PH domains and Src-targeted tyrosines are dispensable. Importantly, in TPC1 thyroid papillary carcinoma cells, silencing endogenous XB130 decreased the rate of wound closure, inhibited matrigel invasion, reduced lamellipodial persistence and slowed down spreading. Thus, XB130 is a novel Rac- and cytoskeleton-regulated and cytoskeleton-regulating Adaptor Protein that exhibits high affinity to lamellipodial (branched) F-actin and impacts motility and invasiveness of tumor cells.
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XB130, a novel Adaptor Protein for signal transduction.
The Journal of biological chemistry, 2007Co-Authors: Xiaohui Bai, Monika Lodyga, Bing Han, Helan Xiao, Shaf Keshavjee, Haibo Zhang, Burton B. Yang, Mingyao LiuAbstract:Abstract Adaptor Proteins are important mediators in signal transduction. In the present study, we report the cloning and characterization of a novel Adaptor Protein, XB130. This gene is located on human chromosome 10q25.3 and encodes a Protein of 818 amino acids. It contains several Src homology (SH)2- and SH3-binding motifs, two pleckstrin homology domains, a coiled-coil region, and a number of potential tyrosine or serine/threonine phosphorylation sites. Endogenous XB130 interacts with c-Src tyrosine kinase. Their co-expression in COS-7 cells resulted in activation of c-Src and elevated tyrosine phosphorylation of multiple Proteins, including XB130 itself. XB130 expression in HEK293 cells enhanced serum response element- and AP-1-dependent transcriptional activation mediated by c-Src. XB130ΔN, an N-terminal deletion mutant lacking a putative SH3-binding motif and several putative SH2-binding sites, reduced its ability to mediate Src signal transduction. Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3β, and altered cell cycles in human lung epithelial cells. These data suggest that XB130 as an Adaptor may play an important role in the regulation of signal transduction and cellular functions.
Hassan Jumaa - One of the best experts on this subject based on the ideXlab platform.
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Dual role of the Adaptor Protein SLP-65
Immunologic Research, 2006Co-Authors: Sebastian Herzog, Bettina Storch, Hassan JumaaAbstract:B cell development is characterized by a coordinated progression through defined stages that are controlled at several checkpoints. Signals from the pre-B cell receptor (pre-BCR) are essential for regulated transition from the pre-B cell stage. The Adaptor Protein SLP-65 plays a key role in this signaling pathway. Recent findings indicate an additional function of SLP-64 as a tumor suppressor that regulates pre-B cell proliferation. We will discuss here the potential mechanisms by which SLP-65 controls the pre-B cell checkpoint.
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the Adaptor Protein slp 65 acts as a tumor suppressor that limits pre b cell expansion
Nature Immunology, 2003Co-Authors: Alexandra Flemming, Tilman Brummer, Michael Reth, Hassan JumaaAbstract:Mice deficient in the Adaptor Protein SLP-65 (also known as BLNK) have reduced numbers of mature B cells, but an increased pre-B cell compartment. We show here that compared to wild-type cells, SLP-65−/− pre-B cells show an enhanced ex vivo proliferative capacity. This proliferation requires interleukin 7 and expression of the pre-B cell receptor (pre-BCR). In addition, SLP-65−/− mice have a high incidence of pre-B cell lymphoma. Reintroduction of SLP-65 into SLP-65−/− pre-B cells led to pre-BCR down-regulation and enhanced differentiation. Our results indicate that SLP-65 regulates a developmental program that promotes differentiation and limits pre-B cell expansion, thereby acting as a tumor suppressor.
Xiaohui Bai - One of the best experts on this subject based on the ideXlab platform.
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XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis
Scientifica, 2014Co-Authors: Xiaohui Bai, Hae-ra Cho, Serisha Moodley, Mingyao LiuAbstract:Several Adaptor Proteins have previously been shown to play an important role in the promotion of tumourigenesis. XB130 (AFAP1L2) is an Adaptor Protein involved in many cellular functions, such as cell survival, cell proliferation, migration, and gene and miRNA expression. XB130's functional domains and motifs enable its interaction with a multitude of Proteins involved in several different signaling pathways. As a tyrosine kinase substrate, tyrosine phosphorylated XB130 associates with the p85α regulatory subunit of phosphoinositol-3-kinase (PI3K) and subsequently affects Akt activity and its downstream signalling. Tumourigenesis studies show that downregulation of XB130 expression by RNAi inhibits tumor growth in mouse xenograft models. Furthermore, XB130 affects tumor oncogenicity by regulating the expression of specific tumour suppressing miRNAs. The expression level and pattern of XB130 has been studied in various human tumors, such as thyroid, esophageal, and gastric cancers, as well as, soft tissue tumors. Studies show the significant effects of XB130 in tumourigenesis and suggest its potential as a diagnostic biomarker and therapeutic target for cancer treatments.
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xb130 a novel Adaptor Protein promotes thyroid tumor growth
American Journal of Pathology, 2011Co-Authors: Atsushi Shiozaki, Monika Lodyga, Xiaohui Bai, Shaf Keshavjee, Jeya Nadesalingam, Takeshi Oyaizu, Daniel A Winer, Sylvia L Asa, Mingyao LiuAbstract:Adaptor Proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel Adaptor Protein, XB130, which binds the p85α subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G 1 -S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the top-ranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators.
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Adaptor Protein xb130 is a rac controlled component of lamellipodia that regulates cell motility and invasion
Journal of Cell Science, 2010Co-Authors: Monika Lodyga, Xiaohui Bai, Andras Kapus, Mingyao LiuAbstract:XB130 is a newly described cytosolic Adaptor Protein and tyrosine kinase substrate, involved in Src- and RET/PTC-dependent signaling. Although XB130 has been cloned as a homologue of actin-filament-associated Protein (AFAP-110), its potential regulation by the actin skeleton and its putative roles in cytoskeleton regulation have not been addressed. Here, we show that XB130 (in contrast to AFAP-110) exhibited robust translocation to the cell periphery in response to various stimuli (including epidermal growth factor, wounding and expression of constitutively active Rac) that elicit lamellipodium formation. In stimulated cells, XB130 localized to the lamellipodial F-actin meshwork. Genetic and pharmacological data suggest that the key trigger for XB130 recruitment is the formation of the branched F-actin itself. Structure-function analysis revealed that both the XB130 N-terminus (167 amino acids) and C-terminus (63 amino acids) harbor crucial regions for its translocation to lamellipodia, whereas the PH domains and Src-targeted tyrosines are dispensable. Importantly, in TPC1 thyroid papillary carcinoma cells, silencing endogenous XB130 decreased the rate of wound closure, inhibited matrigel invasion, reduced lamellipodial persistence and slowed down spreading. Thus, XB130 is a novel Rac- and cytoskeleton-regulated and cytoskeleton-regulating Adaptor Protein that exhibits high affinity to lamellipodial (branched) F-actin and impacts motility and invasiveness of tumor cells.
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XB130, a novel Adaptor Protein for signal transduction.
The Journal of biological chemistry, 2007Co-Authors: Xiaohui Bai, Monika Lodyga, Bing Han, Helan Xiao, Shaf Keshavjee, Haibo Zhang, Burton B. Yang, Mingyao LiuAbstract:Abstract Adaptor Proteins are important mediators in signal transduction. In the present study, we report the cloning and characterization of a novel Adaptor Protein, XB130. This gene is located on human chromosome 10q25.3 and encodes a Protein of 818 amino acids. It contains several Src homology (SH)2- and SH3-binding motifs, two pleckstrin homology domains, a coiled-coil region, and a number of potential tyrosine or serine/threonine phosphorylation sites. Endogenous XB130 interacts with c-Src tyrosine kinase. Their co-expression in COS-7 cells resulted in activation of c-Src and elevated tyrosine phosphorylation of multiple Proteins, including XB130 itself. XB130 expression in HEK293 cells enhanced serum response element- and AP-1-dependent transcriptional activation mediated by c-Src. XB130ΔN, an N-terminal deletion mutant lacking a putative SH3-binding motif and several putative SH2-binding sites, reduced its ability to mediate Src signal transduction. Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3β, and altered cell cycles in human lung epithelial cells. These data suggest that XB130 as an Adaptor may play an important role in the regulation of signal transduction and cellular functions.
Raif S Geha - One of the best experts on this subject based on the ideXlab platform.
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impaired viability and profound block in thymocyte development in mice lacking the Adaptor Protein slp 76
Cell, 1998Co-Authors: Vadim I Pivniouk, Erdyni N Tsitsikov, Paul Swinton, Gary Rathbun, Raif S GehaAbstract:Abstract The Adaptor Protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation. SLP-76-deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4 + 8 + thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.
Stephen J. Mcsorley - One of the best experts on this subject based on the ideXlab platform.
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expression of toll il 1r domain containing Adaptor Protein tirap is detrimental to primary clearance of salmonella and is not required for the generation of protective immunity
Immunology Letters, 2008Co-Authors: Stu Jerke, Aparna Srinivasan, Stephen J. McsorleyAbstract:Salmonella infection triggers activation of innate immune cells through the interaction of bacterial products with Toll-like receptors (TLRs). Toll/IL-1R domain-containing Adaptor Protein (TIRAP) is an Adaptor Protein involved in downstream signaling through TLRs 1, 2, 4, and 6. We examined the role of TIRAP during infection with attenuated Salmonella. Surprisingly, TIRAP-deficient mice were fully capable of resolving primary infection with Salmonella and actually exhibited accelerated clearance of bacteria at a late stage of the infection. Consistent with enhanced bacterial clearance, TIRAP-deficient mice resolved bacterial-associated splenic inflammation more rapidly than wild-type (Wt) mice and splenocytes from Salmonella-infected TIRAP-deficient mice produced more IFN-γ upon in vitro re-stimulation. Upon secondary challenge, TIRAP-deficient and Wt mice displayed a similar level of protective immunity against virulent Salmonella. Together these data indicate that TIRAP-mediated signaling is completely dispensable for clearance of Salmonella infection, and actually has a mild deleterious effect upon the resolution of primary infection.
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Expression of Toll/IL-1R domain-containing Adaptor Protein (TIRAP) is detrimental to primary clearance of Salmonella and is not required for the generation of protective immunity
Immunology Letters, 2008Co-Authors: Stu Jerke, Aparna Srinivasan, Stephen J. McsorleyAbstract:Salmonella infection triggers activation of innate immune cells through the interaction of bacterial products with Toll-like receptors (TLRs). Toll/IL-1R domain-containing Adaptor Protein (TIRAP) is an Adaptor Protein involved in downstream signaling through TLRs 1, 2, 4, and 6. We examined the role of TIRAP during infection with attenuated Salmonella. Surprisingly, TIRAP-deficient mice were fully capable of resolving primary infection with Salmonella and actually exhibited accelerated clearance of bacteria at a late stage of the infection. Consistent with enhanced bacterial clearance, TIRAP-deficient mice resolved bacterial-associated splenic inflammation more rapidly than wild-type (Wt) mice and splenocytes from Salmonella-infected TIRAP-deficient mice produced more IFN-γ upon in vitro re-stimulation. Upon secondary challenge, TIRAP-deficient and Wt mice displayed a similar level of protective immunity against virulent Salmonella. Together these data indicate that TIRAP-mediated signaling is completely dispensable for clearance of Salmonella infection, and actually has a mild deleterious effect upon the resolution of primary infection.
