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Shp1 OR Shp2

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https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#1
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28210822/plasma-dna-methylation-of-p16-and-shp1-in-patients-with-b-cell-non-hodgkin-lymphoma
#2
Kai Ding, Xiaoshuang Chen, Yihao Wang, Hui Liu, Wenjing Song, Lijuan Li, Guojin Wang, Jia Song, Zonghong Shao, Rong Fu
BACKGROUND: Early diagnosis and treatment of non-Hodgkin lymphoma (NHL) are progressively important. It has been shown that aberrant promoter methylation contributes to the development and progression of lymphoma. We tried to explore the effect of methylation of p16 and shp1 genes in plasma in the diagnosis of B-NHL patients. METHODS: The methylation of p16 and shp1 genes in plasma were detected by methylation specific polymerase chain reaction in 103 patients with B-NHL, and compared with peripheral blood leukocytes (PBLs) and formaldehyde-fixed paraffin-embedded (FFPE) tumor tissues...
February 16, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28209599/role-of-shp2-protein-tyrosine-phosphatase-in-sert-inhibition-by-enteropathogenic-e-coli-epec
#3
Megha Singhal, Christopher Manzella, Vinay Soni, Waddah A Alrefai, Seema Saksena, Gail A Hecht, Pradeep K Dudeja, Ravinder K Gill
Enteropathogenic E. coli (EPEC), one of the diarrheagenic E. coli pathotypes, is among the most important food-borne pathogens infecting children worldwide. Inhibition of serotonin transporter (SERT), that regulates extracellular availability of serotonin (5-HT), has been previously implicated in EPEC-associated diarrhea. EPEC was shown to inhibit SERT via activation of protein tyrosine phosphatases (PTPase), albeit the specific PTPase involved is not known. Current studies aimed to identify EPEC activated PTPase and its role in SERT inhibition...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28208810/shp2-plays-a-critical-role-in-il-6-induced-emt-in-breast-cancer-cells
#4
Xuan Sun, Jie Zhang, Zhiyong Wang, Wei Ji, Ran Tian, Fei Zhang, Ruifang Niu
Accumulative evidence demonstrates that the protein tyrosine phosphatase Shp2 functions as a powerful tumor promoter in many types of cancers. Abnormal expression of Shp2 has been implicated in many human malignancies. Overexpression of Shp2 in cancer tissues is correlated with cancer metastasis, resistance to targeted therapy, and poor prognosis. The well-known function of Shp2 is its positive role in regulating cellular signaling initiated by growth factors and cytokines, including interleukin-6 (IL-6). Several recent studies have shown that Shp2 is required for epithelial-mesenchymal transition (EMT), triggered by growth factors...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202316/an-epigenetic-modifier-induces-production-of-10-s-verruculide-b-an-inhibitor-of-protein-tyrosine-phosphatases-by-phoma-sp-nov-lg0217-a-fungal-endophyte-of-parkinsonia-microphylla
#5
Juliana R Gubiani, E M Kithsiri Wijeratne, Taoda Shi, Angela R Araujo, A Elizabeth Arnold, Eli Chapman, A A Leslie Gunatilaka
Incorporation of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), to a culture broth of the endophytic fungus Phoma sp. nov. LG0217 isolated from Parkinsonia microphylla changed its metabolite profile and resulted in the production of (10'S)-verruculide B (1), vermistatin (2) and dihydrovermistatin (3). When cultured in the absence of the epigenetic modifier, it produced a new metabolite, (S,Z)-5-(3',4'-dihydroxybutyldiene)-3-propylfuran-2(5H)-one (4) together with nafuredin (5)...
February 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28159016/%C3%AE-2ap-regulates-vascular-alteration-by-inhibiting-vegf-signaling-in-systemic-sclerosis-the-roles-of-%C3%AE-2ap-in-vascular-dysfunction-in-systemic-sclerosis
#6
Yosuke Kanno, En Shu, Hiroyuki Kanoh, Ayaka Matsuda, Mariko Seishima
BACKGROUND: Systemic sclerosis (SSc) is a connective tissues disease of unknown origin characterized by vascular damage and extensive fibrosis. Recently, we demonstrated that α2-antiplasmin (α2AP) is associated with the development of fibrosis in SSc. We herein investigate the roles of α2AP in vascular dysfunction in SSc. METHODS: Vascular damage in mice was determined by the levels of blood vessels and blood flow. Vascular functions in vascular endothelial cells (ECs) were determined by the levels of tube formation, cell proliferation, and endothelial junction-associated protein (VE-cadherin and PECAM1) production...
February 3, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28115166/gab3-is-required-for-human-colorectal-cancer-cell-proliferation
#7
Shihao Xiang, Na Wang, Pingping Hui, Jiali Ma
Here, we focused on the potential function of Gab3, an uncommon Gab family protein, in human colorectal cancer (CRC) cells. We found that Gab3 was only expressed in human colon cancer tissues as well as in established (HCT-116 and HT-29 lines) and primary human CRC cells. It was however absent in normal human colon cancer tissues and in FHC colon epithelial cells. Knockdown of Gab3 by targeted-shRNAs inhibited proliferation of the CRC cells. Reversely, exogenous over-expression of Gab3 promoted CRC cell proliferation...
January 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28074573/structural-functional-and-clinical-characterization-of-a-novel-ptpn11-mutation-cluster-underlying-noonan-syndrome
#8
Luca Pannone, Gianfranco Bocchinfuso, Elisabetta Flex, Cesare Rossi, Giuseppina Baldassarre, Christina Lissewski, Francesca Pantaleoni, Federica Consoli, Francesca Lepri, Monia Magliozzi, Massimiliano Anselmi, Giovanni Sorge, Kadri Karaer, Goran Cuturilo, Alessandro Sartorio, Sigrid Tinschert, Maria Accadia, Maria C Digilio, Giuseppe Zampino, Alessandro De Luca, Hélène Cavé, Martin Zenker, Bruce D Gelb, Bruno Dallapiccola, Lorenzo Stella, Giovanni B Ferrero, Simone Martinelli, Marco Tartaglia
Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu(261) , Leu(262) and Arg(265) in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling...
January 10, 2017: Human Mutation
https://www.readbyqxmd.com/read/28059452/shp2-promotes-liver-cancer-stem-cell-expansion-by-augmenting-%C3%AE-catenin-signaling-and-predicts-chemotherapeutic-response-of-patients
#9
Daimin Xiang, Zhuo Cheng, Hui Liu, Xue Wang, Tao Han, Wen Sun, Xiaofeng Li, Wen Yang, Cheng Chen, Mingyang Xia, Na Liu, Shengyong Yin, Guangzhi Jin, Terence Lee, Liwei Dong, Heping Hu, Hongyang Wang, Jin Ding
: Src-homology 2 domain-containing phosphatase 2 (Shp2) has been reported to play an important role in the maintenance and self-renewal of embryonic and adult stem cells, but its role in cancer stem cells (CSCs) remains obscure. Herein, we observed high expression of Shp2 in both chemoresistant hepatocellular carcinomas (HCCs) and recurrent HCCs from patients. A remarkable increase of Shp2 was detected in sorted epithelial cell adhesion molecule-positive or cluster of differentiation 133-positive liver CSCs and in CSC-enriched hepatoma spheroids from patients...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28035977/shp2-socs3-and-pias3-expression-patterns-in-medulloblastomas-relevance-to-stat3-activation-and-resveratrol-suppressed-stat3-signaling
#10
Cong Li, Hong Li, Peng Zhang, Li-Jun Yu, Tian-Miao Huang, Xue Song, Qing-You Kong, Jian-Li Dong, Pei-Nan Li, Jia Liu
BACKGROUND: Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. METHODS: Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation...
December 27, 2016: Nutrients
https://www.readbyqxmd.com/read/28035384/correlative-analyses-of-the-expression-levels-of-pias3-p-shp2-socs1-and-socs3-with-stat3-activation-in-human-astrocytomas
#11
Li-Hong Liu, Hong Li, Xiao-Xin Cheng, Qing-You Kong, Xiao-Yan Chen, Mo-Li Wu, Yan Li, Jia Liu, Cong Li
The importance of signal transducer and activator of transcription 3 (STAT3) signaling in the growth and survival of glioblastoma cells has been well documented, while the reasons leading to STAT3 activation remains to be elucidated. Suppressors of cytokine signaling (SOCS) 1 and SOCS3, SH2 domain‑containing phosphatase (SHP2) and protein inhibitors of activated STAT3 (PIAS3) are known to inhibit STAT3 signal transduction, while their expression statuses in the four grades of astrocytomas and relevance with STAT3 activation remain to be described...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27997991/decreased-frequencies-and-impaired-functions-of-the-cd31-subpopulation-in-treg-cells-associated-with-decreased-foxp3-expression-and-enhanced-treg-cell-defects-in-patients-with-coronary-heart-disease
#12
L Huang, Y Zheng, X Yuan, Y Ma, G Xie, W Wang, H Chen, L Shen
Coronary heart disease (CHD) is one of the most common types of organ lesions caused by atherosclerosis, in which CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+) ) regulatory T cells (Treg ) play an atheroprotective role. However, Treg cell numbers are decreased and their functions are impaired in atherosclerosis; the underlying mechanisms remain unclear. CD31 plays an important part in T cell response and contributes to maintaining T cell tolerance. The immunomodulatory effects of CD31 are also implicated in atherosclerosis...
March 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27974211/dual-shp2-and-pten-deficiencies-promote-non-alcoholic-steatohepatitis-and-genesis-of-liver-tumor-initiating-cells
#13
Xiaolin Luo, Rui Liao, Kaisa L Hanley, Helen He Zhu, Kirsten N Malo, Carolyn Hernandez, Xufu Wei, Nissi M Varki, Nazilla Alderson, Catherine Chu, Shuangwei Li, Jia Fan, Rohit Loomba, Shuang-Jian Qiu, Gen-Sheng Feng
The complexity of liver tumorigenesis is underscored by the recently observed anti-oncogenic effects of oncoproteins, although the mechanisms are unclear. Shp2/Ptpn11 is a proto-oncogene in hematopoietic cells and antagonizes the effect of tumor suppressor Pten in leukemogenesis. In contrast, we show here cooperative functions of Shp2 and Pten in suppressing hepatocarcinogenesis. Ablating both Shp2 and Pten in hepatocytes induced early-onset non-alcoholic steatohepatitis (NASH) and promoted genesis of liver tumor-initiating cells likely due to augmented cJun expression/activation and elevated ROS and inflammation in the hepatic microenvironment...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27959415/promoter-methylation-attenuates-shp1-expression-and-function-in-patients-with-primary-central-nervous-system-lymphoma
#14
Jing Liu, Yaming Wang, Xuefei Sun, Nan Ji, Shengjun Sun, Yajie Wang, Fusheng Liu, Qu Cui, Chen Wang, Yuanbo Liu
The Src homology region 2 domain-containing phosphatase-1 (SHP1) is a critical negative regulator involved in the JAK/STAT signaling pathway. The SHP1 gene has been proposed as a candidate tumor suppressor in solid and hematological malignancies and promoter methylation is an important biological process in controlling tumorigenesis. However, the detailed roles of SHP1 promoter methylation in the pathogenesis of primary central nervous system lymphoma (PCNSL) is largely unknown. In the present study, we evaluated the correlation between SHP1 expression and promoter methylation in patients with PCNSL...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27942593/low-dose-dasatinib-rescues-cardiac-function-in-noonan-syndrome
#15
Jae-Sung Yi, Yan Huang, Andrea T Kwaczala, Ivana Y Kuo, Barbara E Ehrlich, Stuart G Campbell, Frank J Giordano, Anton M Bennett
Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27939989/identification-of-demethylincisterol-a3-as-a-selective-inhibitor-of-protein-tyrosine-phosphatase-shp2
#16
Chuan Chen, Fan Liang, Bo Chen, Zhongyi Sun, Tongdan Xue, Runlei Yang, Duqiang Luo
Shp2 is a classical non-receptor protein tyrosine phosphatase (PTP) involved in many human diseases such as Noonan syndrome and tumors, and identified as a potential therapeutic target. In order to find a potent and selective Shp2 inhibitor, we screened a diverse collection of the secondary metabolites from endophyte fungi using an in vitro enzyme assay, and finally identified a potent Shp2 inhibitor, HLP46 (demethylincisterol A3) from Pestalotiopsis sp. HLP46 was reported to have anti-tumor and anti-inflammation activity previously...
December 8, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27935860/t-lymphocyte-shp2-deficiency-triggers-anti-tumor-immunity-to-inhibit-colitis-associated-cancer-in-mice
#17
Wen Liu, Wenjie Guo, Lihong Shen, Zhen Chen, Qiong Luo, Xiaolin Luo, GenSheng Feng, Yongqian Shu, Yanhong Gu, Qiang Xu, Yang Sun
Nonresolving inflammation is involved in the initiation and progression process of tumorigenesis. Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is known to inhibit acute inflammation but its role in chronic inflammation-associated cancer remains unclear. The role of SHP2 in T cells in dextran sulfate sodium (DSS)-induced colitis and azoxymethane-DSS-induced colitis-associated carcinogenesis was examined using SHP2CD4-/- conditional knockout mice. SHP2 deficiency in T cells aggravated colitis with increased level of pro-inflammatory cytokines including IFN-γ and IL-17A...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27926479/decline-in-arylsulfatase-b-leads-to-increased-invasiveness-of-melanoma-cells
#18
Sumit Bhattacharyya, Leo Feferman, Kaoru Terai, Arkadiusz Z Dudek, Joanne K Tobacman
Arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) is reduced in several malignancies, but levels in melanoma have not been investigated previously. Experiments were performed in melanoma cell lines to determine ARSB activity and impact on melanoma invasiveness. ARSB activity was reduced ~50% in melanoma cells compared to normal melanocytes. Silencing ARSB significantly increased the mRNA expression of chondroitin sulfate proteoglycan(CSPG)4 and pro-matrix metalloproteinase(MMP)-2, known mediators of melanoma progression...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894814/tanshinone-iia-induced-cell-death-via-mir30b-p53-ptpn11-shp2-signaling-pathway-in-human-hepatocellular-carcinoma-cells
#19
Xuanqi Ren, Cui Wang, Binbin Xie, Linfeng Hu, Hui Chai, Lei Ding, Lihua Tang, Yongliang Xia, Xiaobing Dou
Tanshinone IIA, a multi-pharmaceutical compound from traditional Chinese herb, has been reported to have anti-hepatocarcinomic (HCC) properties through cell death induction. Apart from the typical p53-dependent pathway, mechanisms of the anti-carcinogenic role of Tanshinone remain scarce. In an effort to explore the mechanism behind Tanshinone IIA, we detected the upstream of the p53 and the potential novel pathway. Tanshinone IIA dose-dependently initiated HepG2 cell apoptosis and cell cycle arrest at the G1 checkpoint...
November 26, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27876799/irs4-induces-mammary-tumorigenesis-and-confers-resistance-to-her2-targeted-therapy-through-constitutive-pi3k-akt-pathway-hyperactivation
#20
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, John Hilkens
In search of oncogenic drivers and mechanisms affecting therapy resistance in breast cancer, we identified Irs4, a poorly studied member of the insulin receptor substrate (IRS) family, as a mammary oncogene by insertional mutagenesis. Whereas normally silent in the postnatal mammary gland, IRS4 is found to be highly expressed in a subset of breast cancers. We show that Irs4 expression in mammary epithelial cells induces constitutive PI3K/AKT pathway hyperactivation, insulin/IGF1-independent cell proliferation, anchorage-independent growth and in vivo tumorigenesis...
November 23, 2016: Nature Communications
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