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https://www.readbyqxmd.com/read/28643869/mechanotransduction-properties-of-the-cytoplasmic-tail-of-pecam-1
#1
Jessica L Snyder, Elena McBeath, Tamlyn N Thomas, Yi Jen Chiu, Robert L Clark, Keigi Fujiwara
BACKGROUND: Vascular endothelial cells (ECs) are a well-known cell system used in the study of mechanobiology. Using cultured ECs, we found that platelet endothelial cell adhesion molecule 1 (PECAM-1, CD31), a cell adhesion protein localized to regions of EC-EC contact, was rapidly tyrosine phosphorylated in ECs exposed to shear or cyclic stretch. Src-homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) binds phosphorylated PECAM-1 and activates the extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade, a known flow-activated signaling pathway...
June 23, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28633870/omega-3-free-fatty-acids-attenuate-insulin-promoted-breast-cancer-cell-proliferation
#2
Yang Guo, Sheng-Long Zhu, Yi-Kuan Wu, Zhao He, Yong-Quan Chen
High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28606940/shp1-function-in-myeloid-cells
#3
REVIEW
Clare L Abram, Clifford A Lowell
The motheaten mouse was first described in 1975 as a model of systemic inflammation and autoimmunity, as a result of immune system dysregulation. The phenotype was later ascribed to mutations in the cytoplasmic tyrosine phosphatase Shp1. This phosphatase is expressed widely throughout the hematopoietic system and has been shown to impact a multitude of cell signaling pathways. The determination of which cell types contribute to the different aspects of the phenotype caused by global Shp1 loss or mutation and which pathways within these cell types are regulated by Shp1 is important to further our understanding of immune system regulation...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28599500/notable-roles-of-ezh2-and-dnmt1-in-epigenetic-dormancy-of-the-shp1-gene-during-the-progression-of-chronic-myeloid-leukaemia
#4
Jing Wang, Luoming Hua, Ming Guo, Lin Yang, Xiaojun Liu, Yanmeng Li, Xiaoyan Shang, Jianmin Luo
Tumor development is associated with the methylation of cytosine-guanine (CpG) islands. The occurrence of methylation requires several factors, such as DNA methylation systems and polycomb group (PcG) proteins. At present, novel drugs are needed for the treatment of chronic myeloid leukaemia (CML), particularly considering the current prognosis of CML. The methylation status of the Src homology 2 domain-containing tyrosine phosphatase 1 (SHP1) gene, a negative regulator of signal transduction, has been identified as being altered in numerous haematological malignancies...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28593618/rig-i-a-multifunctional-protein-beyond-a-pattern-recognition-receptor
#5
REVIEW
Xiao-Xiao Xu, Han Wan, Li Nie, Tong Shao, Li-Xin Xiang, Jian-Zhong Shao
It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations...
June 8, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28582432/in-vivo-efficacy-of-the-akt-inhibitor-arq-092-in-noonan-syndrome-with-multiple-lentigines-associated-hypertrophic-cardiomyopathy
#6
Jianxun Wang, Vasanth Chandrasekhar, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Maria I Kontaridis
Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in mice harboring the PTPN11 mutation Y279C, one of the most common NSML alleles; these now-termed SHP2Y279C/+ mice recapitulate the human disorder and develop hypertrophic cardiomyopathy (HCM) by 12 weeks of age...
2017: PloS One
https://www.readbyqxmd.com/read/28551626/lipoic-acid-decreases-the-viability-of-breast-cancer-cells-and-activity-of-ptp1b-and-shp2
#7
Alicja Kuban-Jankowska, Magdalena Gorska-Ponikowska, Michal Wozniak
BACKGROUND: Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. MATERIALS AND METHODS: We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28550197/viral-rna-unprimed-rig-i-restrains-stat3-activation-in-the-modulation-of-regulatory-t-cell-th17-cell-balance
#8
Hui Yang, He-Zhou Guo, Xian-Yang Li, Jian Lin, Wu Zhang, Jun-Mei Zhao, Hong-Xin Zhang, Sai-Juan Chen, Zhu Chen, Jiang Zhu
Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4(+) T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I(-/-) CD4(+) T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28525837/differentially-expressed-jak-stat-signaling-pathway-genes-and-target-micrornas-in-the-spleen-of-necrotic-enteritis-afflicted-chicken-lines
#9
Anh Duc Truong, Deivendran Rengaraj, Yeojin Hong, Cong Thanh Hoang, Yeong Ho Hong, Hyun S Lillehoj
The JAK signal transducer and STAT signaling pathway is an important regulator of cell proliferation, differentiation, survival, motility, apoptosis, immune response, and development. In this study, we used RNA-Sequencing, qRT-PCR, and bioinformatics tools to investigate the differential expression of JAK-STAT pathway genes, their interactions, and regulators in the spleen of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and MD-susceptible line 7.2) induced necrotic enteritis (NE) disease by co-infection with Eimeria maxima and Clostridium perfringens...
May 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28490657/targeting-endogenous-proteins-for-degradation-through-the-affinity-directed-protein-missile-system
#10
Luke J Fulcher, Luke D Hutchinson, Thomas J Macartney, Craig Turnbull, Gopal P Sapkota
Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28483911/cd99-derived-agonist-ligands-inhibit-fibronectin-induced-activation-of-%C3%AE-1-integrin-through-pka-shp2-erk-ptpn12-fak-signaling-pathway
#11
Kyoung-Jin Lee, Yuri Kim, Yeon Ho Yoo, Min-Seo Kim, Sun-Hee Lee, Chang-Gyum Kim, Kyeonghan Park, Dooil Jeoung, Hansoo Lee, In Young Ko, Jang-Hee Hahn
The human CD99 protein is a 32kDa glycosylated transmembrane protein that regulates various cellular responses including cell adhesion and leukocyte extravasation. We previously reported that CD99 activation suppresses β1 integrin activity through dephosphorylation of FAK at Y397. We explored a molecular mechanism underlying the suppression of β1 integrin activity by CD99 agonists and its relevance to tumor growth in vivo CD99-Fc fusion proteins or a series of CD99-derived peptides suppressed β1 integrin activity by specifically interacting with three conserved motifs of the CD99 extracellular domain...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28481957/deletion-of-shp2-in-bronchial-epithelial-cells-impairs-il-25-production-in-vitro-but-has-minor-influence-on-asthmatic-inflammation-in-vivo
#12
Zhangwei Qiu, Jiesen Zhou, Fang Liu, Xuejun Qin, Yuanrong Dai, Yuehai Ke, Zhihua Chen, Wen Li, Songmin Ying, Huahao Shen
Shp2 played an important role in cigarette-smoke-mediated inflammation, surfactant homeostasis and asthmatic airway remodeling. However, whether shp2 plays a key role in epithelium-associated allergic reaction is still unknown. In this study, LPS and OVA were observed to induce the production of IL-25 in bronchial epithelial cells in vitro via the activation of MAPK p38 and JNK. Furthermore, blockage of Shp2 by its specific inhibitor PHPS1 or by siRNA-mediated depletion was found to reduce the production of IL-25 in epithelial cells as well as the up-regulated LPS-triggered activation of JNK but not p38...
2017: PloS One
https://www.readbyqxmd.com/read/28465343/itim-receptors-more-than-just-inhibitors-of-platelet-activation
#13
Carmen H Coxon, Mitchell J Geer, Yotis A Senis
Since their discovery, immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors have been shown to inhibit signaling from immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors in almost all hematopoietic cells, including platelets. However, a growing body of evidence has emerged demonstrating that this is an over-simplification, and that ITIM-containing receptors are versatile regulators of platelet signal transduction, with functions beyond inhibiting ITAM-mediated platelet activation...
May 2, 2017: Blood
https://www.readbyqxmd.com/read/28463680/loss-of-ptpn11-shp2-drives-satellite-cells-into-quiescence
#14
Joscha Griger, Robin Schneider, Ines Lahmann, Verena Schöwel, Charles Keller, Simone Spuler, Marc Nazare, Carmen Birchmeier
The equilibrium between proliferation and quiescence of myogenic progenitor and stem cells is tightly regulated to ensure appropriate skeletal muscle growth and repair. The non-receptor tyrosine phosphatase Ptpn11 (Shp2) is an important transducer of growth factor and cytokine signals. Here we combined complex genetic analyses, biochemical studies and pharmacological interference to demonstrate a central role of Ptpn11 in postnatal myogenesis of mice. Loss of Ptpn11 drove muscle stem cells out of the proliferative and into a resting state during muscle growth...
May 2, 2017: ELife
https://www.readbyqxmd.com/read/28460481/shp2-is-induced-by-the-hbx-nf-%C3%AE%C2%BAb-pathway-and-contributes-to-fibrosis-during-human-early-hepatocellular-carcinoma-development
#15
Hyo Jeong Kang, Dal-Hee Chung, Chang Ohk Sung, Su Hyun Yoo, Eunsil Yu, Nayoung Kim, Sy-Hye Lee, Ji-Young Song, Chong Jai Kim, Jene Choi
The non-receptor tyrosine phosphatase SHP2 has scaffolding functions in signal transduction cascades downstream of growth receptors. A recent study suggested that SHP2 acts as a tumor suppressor during hepatocellular carcinoma (HCC) development. Herein we examined whether SHP2 links the HBx-NF-κB pathway to EGFR signaling during HCC development. The overexpression of HBx or NF-κB led to increased SHP2 expression via NF-κB binding to the Shp2 promoter. EGF treatment induced ERK activation as well as the rapid assembly of SHP2, EGFR, and Gab1...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424251/nuclear-shp2-directs-normal-embryo-implantation-via-facilitating-the-er%C3%AE-tyrosine-phosphorylation-by-the-src-kinase
#16
Hao Ran, Shuangbo Kong, Shuang Zhang, Jianghong Cheng, Chan Zhou, Bo He, Qiliang Xin, John P Lydon, Francesco J DeMayo, Gen-Sheng Feng, Guoliang Xia, Zhongxian Lu, Chao Wang, Haibin Wang
Estrogen and progesterone coupled with locally produced signaling molecules are essential for embryo implantation. However, the hierarchical landscape of the molecular pathways that governs this process remains largely unexplored. Here we show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK signaling, is predominately localized in the nuclei in the periimplantation mouse uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor (PR) expression and progesterone resistance, which derails normal uterine receptivity, leading to complete implantation failure in mice...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28423588/shp2-confers-cisplatin-resistance-in-small-cell-lung-cancer-via-an-akt-mediated-increase-in-ca916798
#17
Xuemei Yang, Chunlan Tang, Hu Luo, Haijing Wang, Xiangdong Zhou
The tyrosine phosphatase Shp2 is associated with tumorigenesis in small cell lung cancer (SCLC). However, the relationship between Shp2 and resistance to chemotherapy remains unclear. Here, we show that Shp2 plays an important role in inducing resistance to cisplatin-based chemotherapy via the SHP2-AKT-CA916798 pathway. In an SCLC cell line, overexpression of Shp2 induced cisplatin resistance and the increased expression of AKT, pAKT, pmTOR, and CA916798. Conversely, depletion of Shp2 in a cisplatin-resistant cell line via RNA interference increased cisplatin sensitivity and decreased AKT, pAKT, pmTOR, and CA916798 expression levels...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416389/shp1-positively-regulates-egfr-signaling-by-controlling-egfr-protein-expression-in-mammary-epithelial-cells
#18
Taichang Yuan, Hua Ma, Zhuanyun Du, Xusheng Xiong, Hongwei Gao, Zenghui Fang, Licai He, Hongzhi Li, Haihua Gu
SH2-domain containing protein tyrosine phosphatase 1 (Shp1/PTPN6) is mainly expressed in hematopoietic cells and acts a negative signaling regulator. Although Shp1 is also expressed in epithelial cells, the function of shp1 in normal epithelial is still less well understood, especially in regulating the growth of epithelial cells. In this study, different shRNAs and siRNAs against Shp1 were used to knockdown Shp1 expression in MCF10A, an immortalized mammary epithelial cell line. Shp1 knockdown resulted in inhibited cell growth in part due to lower percentage of MCF10A cells entering into S phase and reduced cyclin D1 expression...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28413197/structure-and-function-of-helicobacter-pylori-caga-the-first-identified-bacterial-protein-involved-in-human-cancer
#19
REVIEW
Masanori Hatakeyama
Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor of gastric cancer. The cagA gene-encoded CagA protein is delivered into gastric epithelial cells via bacterial type IV secretion, where it undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Delivered CagA then acts as a non-physiological scaffold/hub protein by interacting with multiple host signaling molecules, most notably the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1/MARK, in both tyrosine phosphorylation-dependent and -independent manners...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28410990/tyrosine-kinase-syk-licenses-myd88-adaptor-protein-to-instigate-il-1%C3%AE-mediated-inflammatory-disease
#20
Prajwal Gurung, Gaofeng Fan, John R Lukens, Peter Vogel, Nicholas K Tonks, Thirumala-Devi Kanneganti
Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6(spin) mice) develop an inflammatory skin disease that resembles neutrophilic dermatosis in humans. Here, we demonstrated that interleukin-1α (IL-1α) signaling through IL-1R and MyD88 in both stromal and immune cells drive inflammation in Ptpn6(spin) mice. We further identified SYK as a critical kinase that phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis in Ptpn6(spin) mice. Our studies further demonstrated that SHP1 encoded by Ptpn6 binds and suppresses SYK activation to inhibit MyD88 phosphorylation...
April 18, 2017: Immunity
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