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SRC Antibody - N-Terminal Region (ARP32476 P050) Data Sheet
SRC antibody - N-terminal region (ARP32476_P050) Data Sheet Product Number ARP32476_P050 Product Name SRC antibody - N-terminal region (ARP32476_P050) Size 50ug Gene Symbol SRC Alias Symbols ASV; SRC1; c-SRC; p60-Src Nucleotide Accession# NM_005417 Protein Size (# AA) 536 amino acids Molecular Weight 60kDa Product Format Lyophilized powder NCBI Gene Id 6714 Host Rabbit Clonality Polyclonal Official Gene Full Name V-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) Gene Family SH2D This is a rabbit polyclonal antibody against SRC. It was validated on Western Blot by Aviva Systems Biology. At Aviva Systems Biology we manufacture rabbit polyclonal antibodies on a large scale (200-1000 Description products/month) of high throughput manner. Our antibodies are peptide based and protein family oriented. We usually provide antibodies covering each member of a whole protein family of your interest. We also use our best efforts to provide you antibodies recognize various epitopes of a target protein. For availability of antibody needed for your experiment, please inquire (). Peptide Sequence Synthetic peptide located within the following region: QTPSKPASADGHRGPSAAFAPAAAEPKLFGGFNSSDTVTSPQRAGPLAGG This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the Description of Target regulation of embryonic development and cell growth. SRC protein is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the -
Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent -
Review Tec Kinases: a Family with Multiple Roles in Immunity
Immunity, Vol. 12, 373±382, April, 2000, Copyright 2000 by Cell Press Tec Kinases: A Family Review with Multiple Roles in Immunity Wen-Chin Yang,*³§ Yves Collette,*³ inositol phosphates, but they are thought to be relevant Jacques A. NuneÁ s,*³ and Daniel Olive*² for binding of PtdIns lipids to the same sites. In most *INSERM U119 cases, PH domains bind preferentially to PtdIns (4,5)P2 Universite de la Me diterrane e and inositol (1,4,5) P3 (Ins (1,4,5) P3). However, the Btk 13009 Marseille PH domain binds PtdIns (3,4,5)P3 and Ins (1, 3, 4, 5)P4 France the tightest. PtdIns (3, 4, 5)P3, one of the products of the action of PI3K, is thought to act as a second messen- ger to recruit regulatory proteins to the plasma mem- brane via their PH domains (see below). Many of the Antigen receptors on T, B, and mast cells are multimo- mutations in Btk that lead to XLA are point mutations lecular complexes that are activated by interactions with that cluster at one end of the PH domain and could be external signals. These signals are then transmitted to predicted to impair binding to Ins (3,4,5)P (for review regulate gene expression and posttranscriptional modi- 3 see Satterthwaite et al., 1998a) (Figure 1b). Similarly, fications. Nonreceptor tyrosine kinases (NRTK) are key CBA/N xid mice carry an R28C mutation in the Btk PH players that relay and integrate these signals. NRTK are domain. The recent structure of the PH domain from divided into distinct families defined by a prototypic Btk complexed with Ins (1,3,4,5)P4 provides an explana- member: Src, Tec, Syk, Csk, Fes, Abl, Jak, Fak, Ack, tion for several mutations associated with XLA: mis- Brk, and Srm (Bolen and Brugge, 1997). -
Assessing the Tumor Microenvironment by Recovery of Immune Receptor V(D)J Recombination Reads from Tumor Specimen Exome Files
Assessing the Tumor Microenvironment by Recovery of Immune Receptor V(D)J Recombination Reads from Tumor Specimen Exome Files George Blanck, Ph.D. Professor, Molecular Medicine Morsani College of Medicine, USF Immunology Program, Moffitt Cancer Center (not for publication or public web page) Learning objectives: 1. To appreciate the availability of T-cell receptor recombination information from tumor specimen DNA samples. 2. To understand the correlation between T-cell receptor recombinations, in tumor specimen DNA, and other, clinically relevant information for bladder cancer and kidney renal cell carcinoma. 3. To understand the importance of HLA alleles in assessing the impact of T-cell receptor recombinations from tumor specimen DNA. Fig. 1. Immune receptor genes recombine during development to generate many different receptor molecules among the B-cells and T- cells, throughout the body, through life, to bind many different antigens, including tumor antigens. Seven immune receptor genes total: • Three related to antibodies, not further discussed. • Two related to gamma-delta T-cells, not further discussed • Two required for alpha-beta T-cells, the subject of this presentation. Alpha-beta T-cells: • Most numerous. • Best understood, medically speaking. • Generally target peptide antigen, in the case of tumors, a mutant peptide. • The TRB part of the TRA/TRB receptor is considered most important in antigen binding. The tumor specimen and the exome • Surgically remove tumor, obtain DNA sequence (all exons = exome), for tumor mutations, which can guide therapy. • Other cells in the specimen, particularly T-cells. • The DNA representing the T-cell receptor can be identified above the tumor DNA “background”. Fig. -
Transcriptional Control of Tissue-Resident Memory T Cell Generation
Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2019 © 2019 Filip Cvetkovski All rights reserved ABSTRACT Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation. In addition, the gene expression profile of lung CD4+TRM was enriched in gene sets previously described in tissue-resident regulatory T cells. Up-regulation of immunomodulatory molecules such as CTLA-4, PD-1, and ICOS, suggested a potential regulatory role for CD4+TRM in tissues. Using loss-of-function genetic experiments in mice, we demonstrate that IRF4 is required for the generation of lung-localized pathogen-specific effector CD4+T cells during acute influenza infection. Influenza-specific IRF4−/− T cells failed to fully express CD44, and maintained high levels of CD62L compared to wild type, suggesting a defect in complete differentiation into lung-tropic effector T cells. -
Transcriptional Regulation of Kinases Downstream of the T Cell Receptor
Petrillo et al. BMC Pharmacology and Toxicology 2014, 15:35 http://www.biomedcentral.com/2050-6511/15/35 RESEARCH ARTICLE Open Access Transcriptional regulation of kinases downstream of the T cell receptor: another immunomodulatory mechanism of glucocorticoids Maria Grazia Petrillo1†, Katia Fettucciari2†, Paolo Montuschi3†, Simona Ronchetti1, Luigi Cari1, Graziella Migliorati1, Emanuela Mazzon4, Oxana Bereshchenko1, Stefano Bruscoli1, Giuseppe Nocentini1,5* and Carlo Riccardi1 Abstract Background: Glucocorticoids affect peripheral immune responses, including modulation of T-cell activation, differentiation, and apoptosis. The quantity and quality of T-cell receptor (TCR)-triggered intracellular signals modulate T-cell function. Thus, glucocorticoids may affect T cells by interfering with the TCR signaling cascade. The purpose of the study was to search for glucocorticoid-modulated kinases downstream of the TCR. Methods: Gene modulation in lymphoid cells either treated with glucocorticoids or from glucocorticoid-treated mice was studied using a RNase protection assay, real-time PCR, and western blotting. The sensitivity of genetically modified thymocytes to glucocorticoid-induced apoptosis was studied by performing hypotonic propidium iodide staining and flow cytometry. The Student’s t-test was employed for statistical evaluation. Results: We found that transcription of Itk, a non-receptor tyrosine kinase of the Tec family, was up-regulated in a mouse T-cell hybridoma by the synthetic glucocorticoid dexamethasone. In contrast, dexamethasone down-regulated the expression of Txk, a Tec kinase that functions redundantly with Itk, and Lck, the Src kinase immediately downstream of the TCR. We investigated the expression of Itk, Txk,andLck in thymocytes and mature lymphocytes following in vitro and in vivo dexamethasone treatment at different time points and doses. -
A New Role for NKG2D Signaling in CD8 T Cells and Autoimmune
A new role for NKG2D signaling in CD8+ T cells and autoimmune diabetes By Andrew P Trembath © 2019 Submitted to the graduate degree program in Microbiology, Molecular Genetics and Immunology, and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Chair: Mary A. Markiewicz Ph.D Wolfram R. Zückert Ph.D. Patrick E. Fields, Ph.D. Maria Kalamvoki Ph.D. Joe Lutkenhaus Ph.D Date Defended: 11/13/2019 ii The dissertation committee for Andrew Trembath certifies that this is the approved version of the following dissertation: A new role for NKG2D signaling in CD8+ T cells and autoimmune diabetes Chair: Mary A. Markiewicz, Ph.D. Date Approved: 12/19/2019 iii Abstract The demands placed on the immune system are immense and highly complex. It must protect the body against untold threats while maintaining a balance between immune defense and autoimmune damage. One major player in immune recognition is the receptor Natural-Killer- Group-2-Member-D (NKG2D), best known for its expression on natural killer (NK) cells and CD8+ T cells, where it recognizes NKG2D ligands expressed by stressed cells following viral infection or cancerous transformation. NKG2D is most well studied for its role in tumor immunity, for which NKG2D based therapies are currently being developed clinically. Despite this, it is apparent that NKG2D has other poorly understood immune regulating functions, such as its implicated involvement in type 1diabetes and other autoimmune disorders. However, the mechanism by which NKG2D signaling affects diabetes has been unclear. We therefore sought to further clarify the role NKG2D plays in autoimmune diabetes development. -
Toll and Toll-Like Receptor Signalling in Development Niki Anthoney*, Istvan Foldi‡ and Alicia Hidalgo§
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repository of the Academy's Library © 2018. Published by The Company of Biologists Ltd | Development (2018) 145, dev156018. doi:10.1242/dev.156018 DEVELOPMENT AT A GLANCE Toll and Toll-like receptor signalling in development Niki Anthoney*, Istvan Foldi‡ and Alicia Hidalgo§ ABSTRACT signalling and discuss how this signalling pathway regulates various The membrane receptor Toll and the related Toll-like receptors aspects of development across species. (TLRs) are best known for their universal function in innate immunity. KEY WORDS: Toll, Tol-1, TLR, TIR-NBS-LRR, Sarm, MyD88, NF-κB, However, Toll/TLRs were initially discovered in a developmental Dorsal, Wek, JNK, FoxO, Cell death, Cell survival, Cell fate, context, and recent studies have revealed that Toll/TLRs carry out Cell proliferation, Structural plasticity, Signalling previously unanticipated functions in development, regulating cell fate, cell number, neural circuit connectivity and synaptogenesis. Introduction Furthermore, knowledge of their molecular mechanisms of action is The Drosophila gene Toll is possibly the only gene associated with expanding and has highlighted that Toll/TLRs function beyond the two Nobel Prizes: it was discovered as one of the key genes canonical NF-κB pathway to regulate cell-to-cell communication and determining body plan, and was later rediscovered for its role in signalling at the synapse. Here, we provide an overview of Toll/TLR underlying innate immunity (leading to the 1995 and 2011 Nobel Prizes in Physiology or Medicine, respectively). Searches for Toll NeuroDevelopment Group, School of Biosciences, University of Birmingham, homologues led to the identification of Toll-like receptor (TLR) Birmingham B15 2TT, UK. -
Src-Family Kinases Impact Prognosis and Targeted Therapy in Flt3-ITD+ Acute Myeloid Leukemia
Src-Family Kinases Impact Prognosis and Targeted Therapy in Flt3-ITD+ Acute Myeloid Leukemia Title Page by Ravi K. Patel Bachelor of Science, University of Minnesota, 2013 Submitted to the Graduate Faculty of School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2019 Commi ttee Membership Pa UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE Commi ttee Membership Page This dissertation was presented by Ravi K. Patel It was defended on May 31, 2019 and approved by Qiming (Jane) Wang, Associate Professor Pharmacology and Chemical Biology Vaughn S. Cooper, Professor of Microbiology and Molecular Genetics Adrian Lee, Professor of Pharmacology and Chemical Biology Laura Stabile, Research Associate Professor of Pharmacology and Chemical Biology Thomas E. Smithgall, Dissertation Director, Professor and Chair of Microbiology and Molecular Genetics ii Copyright © by Ravi K. Patel 2019 iii Abstract Src-Family Kinases Play an Important Role in Flt3-ITD Acute Myeloid Leukemia Prognosis and Drug Efficacy Ravi K. Patel, PhD University of Pittsburgh, 2019 Abstract Acute myelogenous leukemia (AML) is a disease characterized by undifferentiated bone-marrow progenitor cells dominating the bone marrow. Currently the five-year survival rate for AML patients is 27.4 percent. Meanwhile the standard of care for most AML patients has not changed for nearly 50 years. We now know that AML is a genetically heterogeneous disease and therefore it is unlikely that all AML patients will respond to therapy the same way. Upregulation of protein-tyrosine kinase signaling pathways is one common feature of some AML tumors, offering opportunities for targeted therapy. -
The Immune System
Chapter 43 The Immune System Lecture Outline Overview: Reconnaissance, Recognition, and Response • An animal must defend itself against pathogens, infectious agents that cause disease. o Viruses, bacteria, protists, and fungi infect a wide range of animals, including humans. • Animals fight back in various ways. o Immune cells patrol the body fluids of animals, seeking out and destroying foreign cells. o Responses to infection include proteins that punch holes in bacterial membranes or block viruses from entering body cells. • Immune systems help animals to avoid or limit many infections. o External barriers, formed by the skin or shell, provide an obstacle to microbes. o Chemical secretions that trap or kill microbes guard the body’s entrances and exits. o The internal defenses include macrophages and other phagocytic cells that ingest and destroy pathogens. • An animal’s immune system must detect foreign particles and tissues that invade the body, distinguishing self from nonself. • To identify pathogens, animal immune systems use receptors that specifically bind molecules from foreign cells or viruses. • Two general strategies for molecular recognition form the basis for innate and acquired immunity. • Innate immunity is common to all animals. • Innate immune responses are active immediately upon infection and are the same whether or not the pathogen has been encountered previously. • Innate immunity includes the barrier defenses (for example, skin) as well as defenses that combat pathogens after they enter the body. • The activation of many of these internal defenses relies on the recognition of pathogens. o Innate immune cells produce a small, preset group of receptor proteins that accomplish this recognition. -
Supplementary Table 1. in Vitro Side Effect Profiling Study for LDN/OSU-0212320. Neurotransmitter Related Steroids
Supplementary Table 1. In vitro side effect profiling study for LDN/OSU-0212320. Percent Inhibition Receptor 10 µM Neurotransmitter Related Adenosine, Non-selective 7.29% Adrenergic, Alpha 1, Non-selective 24.98% Adrenergic, Alpha 2, Non-selective 27.18% Adrenergic, Beta, Non-selective -20.94% Dopamine Transporter 8.69% Dopamine, D1 (h) 8.48% Dopamine, D2s (h) 4.06% GABA A, Agonist Site -16.15% GABA A, BDZ, alpha 1 site 12.73% GABA-B 13.60% Glutamate, AMPA Site (Ionotropic) 12.06% Glutamate, Kainate Site (Ionotropic) -1.03% Glutamate, NMDA Agonist Site (Ionotropic) 0.12% Glutamate, NMDA, Glycine (Stry-insens Site) 9.84% (Ionotropic) Glycine, Strychnine-sensitive 0.99% Histamine, H1 -5.54% Histamine, H2 16.54% Histamine, H3 4.80% Melatonin, Non-selective -5.54% Muscarinic, M1 (hr) -1.88% Muscarinic, M2 (h) 0.82% Muscarinic, Non-selective, Central 29.04% Muscarinic, Non-selective, Peripheral 0.29% Nicotinic, Neuronal (-BnTx insensitive) 7.85% Norepinephrine Transporter 2.87% Opioid, Non-selective -0.09% Opioid, Orphanin, ORL1 (h) 11.55% Serotonin Transporter -3.02% Serotonin, Non-selective 26.33% Sigma, Non-Selective 10.19% Steroids Estrogen 11.16% 1 Percent Inhibition Receptor 10 µM Testosterone (cytosolic) (h) 12.50% Ion Channels Calcium Channel, Type L (Dihydropyridine Site) 43.18% Calcium Channel, Type N 4.15% Potassium Channel, ATP-Sensitive -4.05% Potassium Channel, Ca2+ Act., VI 17.80% Potassium Channel, I(Kr) (hERG) (h) -6.44% Sodium, Site 2 -0.39% Second Messengers Nitric Oxide, NOS (Neuronal-Binding) -17.09% Prostaglandins Leukotriene, -
Mast Cell Signaling: the Role of Protein Tyrosine Kinase Syk, Its Activation and Screening Methods for New Pathway Participants
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 584 (2010) 4933–4940 journal homepage: www.FEBSLetters.org Review Mast cell signaling: The role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants Reuben P. Siraganian *, Rodrigo O. de Castro, Emilia A. Barbu, Juan Zhang Receptors and Signal Transduction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bldg. 49, Rm. 1A16, Bethesda, MD 20892, USA article info abstract Article history: The aggregation by antigen of the IgE bound to its high affinity receptor on mast cells initiates a Received 27 July 2010 complex series of biochemical events that result in the release of inflammatory mediators. The Accepted 3 August 2010 essential role of the protein tyrosine kinase Syk has been appreciated for some time, and newer Available online 7 August 2010 results have defined the mechanism of its activation. The use of siRNA has defined the relative con- tribution of Syk, Fyn and Gab2 to signaling and has made possible a screening study to identify pre- Edited by Israel Pecht viously unrecognized molecules that are involved in these pathways. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. Keywords: Mast cell FceRI signal transduction Syk Fyn Gab2 Phosphatase 1. Introduction The a-chain binds the Fc portion of IgE at ratio of 1:1 while the b- and c-chains contain ITAMs in their cytoplasmic domains. Be- The activation of mast cells or basophils initiates a series of bio- cause FceRI has no intrinsic enzymatic activity, the activation of chemical events which result in the release of biologically active non-receptor protein tyrosine kinases are essential for cell activa- mediators that cause allergic reactions.