Read by QxMD icon Read

SHP2 brain

Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Maïté Tauber, Hélène Cavé, Marie-Bernadette Delisle
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus...
April 2017: American Journal of Medical Genetics. Part A
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna D Guild, Laura A New, Peihua Lu, Kévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Src homology and collagen (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...
April 7, 2017: Journal of Biological Chemistry
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
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
Gyun Jee Song, Jaehong Kim, Jong-Heon Kim, Seungeun Song, Hana Park, Zhong-Yin Zhang, Kyoungho Suk
Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS)...
October 2016: Experimental Neurobiology
L Zhang, W Zhang, Y Li, A Alvarez, Z Li, Y Wang, L Song, D Lv, I Nakano, B Hu, S-Y Cheng, H Feng
Gliomas are highly malignant brain tumors that are highly invasive and resistant to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRα (platelet-derived growth factor receptor-α), which show frequent aberrant activation in gliomas, are associated with a process of epithelial-mesenchymal transition (EMT), a cellular alteration that confers a more invasive and drug-resistant phenotype. Although this phenomenon is well documented in human cancers, the processes by which RTKs including PDGFRα mediate EMT are largely unknown...
October 27, 2016: Oncogene
Joo Hong Woo, Jee Hoon Lee, Hyunmi Kim, Soo Jung Park, Eun-Hye Joe, Ilo Jou
The term 'inflammation' was first introduced by Celsus almost 2000 years ago. Biological and medical researchers have shown increasing interest in inflammation over the past few decades, in part due to the emerging burden of chronic and degenerative diseases resulting from the increased longevity that has arisen thanks to modern medicine. Inflammation is believed to play critical roles in the pathogenesis of degenerative brain diseases, including Alzheimer's disease and Parkinson's disease. Accordingly, researchers have sought to combat such diseases by controlling inflammatory responses...
June 2015: Experimental Neurobiology
Shinya Kusakari, Fumihito Saitow, Yukio Ago, Koji Shibasaki, Miho Sato-Hashimoto, Yasunori Matsuzaki, Takenori Kotani, Yoji Murata, Hirokazu Hirai, Toshio Matsuda, Hidenori Suzuki, Takashi Matozaki, Hiroshi Ohnishi
Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity...
May 2015: Molecular and Cellular Biology
Yong-Seok Lee, Dan Ehninger, Miou Zhou, Jun-Young Oh, Minkyung Kang, Chuljung Kwak, Hyun-Hee Ryu, Delana Butz, Toshiyuki Araki, Ying Cai, J Balaji, Yoshitake Sano, Christine I Nam, Hyong Kyu Kim, Bong-Kiun Kaang, Corinna Burger, Benjamin G Neel, Alcino J Silva
In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor...
December 2014: Nature Neuroscience
Jussara M do Carmo, Alexandre A da Silva, Sabira E Ebaady, Price O Sessums, Ralph S Abraham, Joel K Elmquist, Bradford B Lowell, John E Hall
Previous studies showed that Src homology-2 tyrosine phosphatase (Shp2) is an important regulator of body weight. In this study, we examined the impact of Shp2 deficiency specifically in proopiomelanocortin (POMC) neurons on metabolic and cardiovascular function and on chronic blood pressure (BP) and metabolic responses to leptin. Mice with Shp2 deleted in POMC neurons (Shp2/Pomc-cre) and control mice (Shp2(flox/flox)) were implanted with telemetry probes and venous catheters for measurement of mean arterial pressure (MAP) and leptin infusion...
December 15, 2014: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Margaret B Allison, Martin G Myers
Hypothalamic leptin action promotes negative energy balance and modulates glucose homeostasis, as well as serving as a permissive signal to the neuroendocrine axes that control growth and reproduction. Since the initial discovery of leptin 20 years ago, we have learned a great deal about the molecular mechanisms of leptin action. An important aspect of this has been the dissection of the cellular mechanisms of leptin signaling, and how specific leptin signals influence physiology. Leptin acts via the long form of the leptin receptor LepRb...
October 2014: Journal of Endocrinology
Li Zhou, Asghar Talebian, Susan O Meakin
The neurotrophins are a family of closely related growth factors that regulate proliferation and differentiation in the developing and mature nervous systems. Neurotrophins stimulate a family of receptor tyrosine kinases (Trk receptors) and utilize an intracellular docking protein termed fibroblast growth factor (FGF) receptor substrate 2 (FRS2) as a major downstream adapter to activate Ras, phosphatidylinositide 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) signaling cascades. The goals of this study were twofold: first, to investigate the complexity of neurotrophin-induced FRS2 interactions in primary cortical neurons and to determine which pathway(s) are important in regulating neuronal growth and, second, to determine whether the related signaling adapter, FRS3, stimulates neuron growth comparable to FRS2...
March 2015: Journal of Molecular Neuroscience: MN
Ritu Mishra, Sunit Kumar Singh
BACKGROUND: Human brain microvascular endothelial cells (hBMVECs) are integral part of the blood brain barrier. Post-translational modifications of adherens junction proteins regulate the permeability of human brain microvascular endothelial cells. Pro-inflammatory signals can induce tyrosine phosphorylation of adherens junction proteins. The primary objective of this work is to provide a molecular model; how the HIV-1 Tat protein can compromise the BBB integrity and eventually lead to neurological consequences...
2014: BMC Neuroscience
Lisa A Ehrman, Diana Nardini, Sarah Ehrman, Tilat A Rizvi, James Gulick, Maike Krenz, Biplab Dasgupta, Jeffrey Robbins, Nancy Ratner, Masato Nakafuku, Ronald R Waclaw
The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities. To gain insight into requirements for Shp2 (LOF) and the impact of abnormal Shp2 GOF mutations, we used a Shp2 conditional mutant allele (LOF) and a cre inducible Shp2-Q79R GOF transgenic mouse in combination with Olig2(cre/+) mice to target embryonic ventral telencephalic progenitors and the oligodendrocyte lineage...
March 5, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Aldarmaa Jalsrai, Tadahiro Numakawa, Yoshiko Ooshima, Naoki Adachi, Hiroshi Kunugi
A variety of flavonoids are suggested to be useful for the treatment of brain-related disorders, including dementia and depression. An investigation on the characteristics of the extracted compounds of Iris tenuifolia Pall. (IT) is of much interest, as this plant has been used as a traditional medicine. In the present study, we examined the effect of total flavonoids obtained from IT on cultured cortical neurons under oxidative-stress and found that pretreatment with IT flavonoids significantly inhibited H 2 O 2-induced cell death in cortical neurons...
2014: American Journal of Chinese Medicine
Tomonori Taniguchi, Shigeru Tanaka, Ayumi Ishii, Miyuki Watanabe, Noriko Fujitani, Ayusa Sugeo, Shuhei Gotoh, Takeshi Ohta, Mineyoshi Hiyoshi, Hideki Matsuzaki, Norio Sakai, Hiroaki Konishi
Grb2-associated regulator of Erk/MAPK1 (GAREM) is an adaptor molecule in the EGF-mediated signaling pathway. GAREM is expressed ubiquitously in human organs and cultured cells. Two GAREM homologues are encoded by the human genome. Therefore, previously identified GAREM is named GAREM1. Here we characterized a new subtype of GAREM, GAREM2, that is specifically expressed in the mouse, rat, and human brain. Three GAREM2 tyrosines (Tyr-102, Tyr-429, and Tyr-551) are phosphorylated upon EGF stimulation and are necessary for binding to Grb2...
October 11, 2013: Journal of Biological Chemistry
M A Gómez del Rio, M I Sánchez-Reus, I Iglesias, M A Pozo, M García-Arencibia, J Fernández-Ruiz, L García-García, M Delgado, J Benedí
Hipericum perforatum is a well-known herbal for its antidepressant property. Recently, it has been shown to have nootropic effects against neurodegenerative disorders. The aim of the present study was to evaluate the protective role of chronic administration of two standardized extract of Hypericum perforatum SHP1 rich in hyperforin (6%) and SHP2 extract poor in hyperforin (0.2%) on the neurodegeneration induced by chronic administration of rotenone in rats. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions...
August 2013: CNS & Neurological Disorders Drug Targets
Manmeet K Mamik, Anuja Ghorpade
CXCL8, one of the first chemokines found in the brain, is upregulated in the brains and cerebrospinal fluid of HIV-1 infected individuals suggesting its potential role in human immune deficiency virus (HIV)-associated neuroinflammation. Astrocytes are known to be the major contributors to the CXCL8 pool. Interleukin (IL)-1β activated astrocytes exhibit significant upregulation of CXCL8. In order to determine the signaling pathways involved in CXCL8 regulation in astrocytes, we employed pharmacological inhibitors for non-receptor Src homology-2 domain-containing protein tyrosine phosphatase (SHP) 2 and mitogen-activated protein kinases (MAPK) pathway and observed reduced expression of CXCL8 following IL-1β stimulation...
2012: PloS One
Toshi Maruyama, Shinya Kusakari, Miho Sato-Hashimoto, Yuriko Hayashi, Takenori Kotani, Yoji Murata, Hideki Okazawa, Per-Arne Oldenborg, Shoji Kishi, Takashi Matozaki, Hiroshi Ohnishi
Signal regulatory protein α (SIRPα) is a neuronal membrane protein that undergoes tyrosine phosphorylation in the brain of mice in response to forced swim (FS) stress in cold water, and this response is implicated in regulation of depression-like behavior in the FS test. We now show that subjection of mice to the FS in warm (37 °C) water does not induce the tyrosine phosphorylation of SIRPα in the brain. The rectal temperature (T(rec) ) of mice was reduced to 27° to 30 °C by performance of the FS for 10 min in cold water, whereas it was not affected by the same treatment in warm water...
June 2012: Journal of Neurochemistry
Emi Kumamaru, Tadahiro Numakawa, Naoki Adachi, Hiroshi Kunugi
Increased glucocorticoids (GCs) have been implicated in the pathophysiology of depressive disorder. We previously found that dexamethasone (DEX, a synthetic GC) repressed brain-derived neurotrophic factor (BDNF)-induced synaptic proteins via suppressing extracellular signal-regulated protein kinase (ERK) signaling. Here, we investigated the possible involvement of Src homology-2 domain-containing phosphatase2 (Shp2), an ERK signaling mediator. We found that DEX suppressed Shp2 interaction with TrkB, a receptor for BDNF, in cultured cortical neurons...
October 20, 2011: FEBS Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"