Type |
Details |
Score |
Publication |
First Author: |
Luo H |
Year: |
2004 |
Journal: |
J Clin Invest |
Title: |
EphB6-null mutation results in compromised T cell function. |
Volume: |
114 |
Issue: |
12 |
Pages: |
1762-73 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lesourne R |
Year: |
2012 |
Journal: |
J Immunol |
Title: |
Interchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function. |
Volume: |
189 |
Issue: |
3 |
Pages: |
1154-61 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wiest DL |
Year: |
1997 |
Journal: |
Immunity |
Title: |
A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. |
Volume: |
6 |
Issue: |
6 |
Pages: |
663-71 |
|
•
•
•
•
•
|
Publication |
First Author: |
Casey SC |
Year: |
2012 |
Journal: |
Mol Endocrinol |
Title: |
The steroid and xenobiotic receptor negatively regulates B-1 cell development in the fetal liver. |
Volume: |
26 |
Issue: |
6 |
Pages: |
916-25 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hikosaka Y |
Year: |
2008 |
Journal: |
Immunity |
Title: |
The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. |
Volume: |
29 |
Issue: |
3 |
Pages: |
438-50 |
|
•
•
•
•
•
|
Publication |
First Author: |
Tamehiro N |
Year: |
2015 |
Journal: |
PLoS One |
Title: |
Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. |
Volume: |
10 |
Issue: |
6 |
Pages: |
e0131047 |
|
•
•
•
•
•
|
Publication |
First Author: |
Liang Y |
Year: |
2013 |
Journal: |
Nat Immunol |
Title: |
The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells. |
Volume: |
14 |
Issue: |
8 |
Pages: |
858-66 |
|
•
•
•
•
•
|
Publication |
First Author: |
The Australian Phenomics Facility at The Australian National University |
Year: |
2006 |
Journal: |
MGI Direct Data Submission |
Title: |
Heritable mouse mutants from the ENU mutagenesis program at the Australian Phenomics Facility at The Australian National University |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Robinson DR |
Year: |
2000 |
Journal: |
Oncogene |
Title: |
The protein tyrosine kinase family of the human genome. |
Volume: |
19 |
Issue: |
49 |
Pages: |
5548-57 |
|
•
•
•
•
•
|
Publication |
First Author: |
Shanghai Model Organisms Center |
Year: |
2017 |
Journal: |
MGI Direct Data Submission |
Title: |
Information obtained from the Shanghai Model Organisms Center (SMOC), Shanghai, China |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2001 |
|
Title: |
Gene Ontology Annotation by the MGI Curatorial Staff |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Lennon G |
Year: |
1999 |
Journal: |
Database Download |
Title: |
WashU-HHMI Mouse EST Project |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Helmholtz Zentrum Muenchen GmbH |
Year: |
2010 |
Journal: |
MGI Direct Data Submission |
Title: |
Alleles produced for the EUCOMM and EUCOMMTools projects by the Helmholtz Zentrum Muenchen GmbH (Hmgu) |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
GOA curators |
Year: |
2016 |
|
Title: |
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Magdaleno S |
Year: |
2006 |
Journal: |
PLoS Biol |
Title: |
BGEM: an in situ hybridization database of gene expression in the embryonic and adult mouse nervous system. |
Volume: |
4 |
Issue: |
4 |
Pages: |
e86 |
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics (MGI) and National Center for Biotechnology Information (NCBI) |
Year: |
2008 |
Journal: |
Database Download |
Title: |
Mouse Gene Trap Data Load from dbGSS |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
GemPharmatech |
Year: |
2020 |
|
Title: |
GemPharmatech Website. |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
UniProt-GOA |
Year: |
2012 |
|
Title: |
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
The Jackson Laboratory Mouse Radiation Hybrid Database |
Year: |
2004 |
Journal: |
Database Release |
Title: |
Mouse T31 Radiation Hybrid Data Load |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Okazaki Y |
Year: |
2002 |
Journal: |
Nature |
Title: |
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. |
Volume: |
420 |
Issue: |
6915 |
Pages: |
563-73 |
|
•
•
•
•
•
|
Publication |
First Author: |
The Gene Ontology Consortium |
Year: |
2010 |
|
Title: |
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2010 |
Journal: |
Database Download |
Title: |
Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Genome U74 Array Platform (A, B, C v2). |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
MGI Genome Annotation Group and UniGene Staff |
Year: |
2015 |
Journal: |
Database Download |
Title: |
MGI-UniGene Interconnection Effort |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2002 |
|
Title: |
Mouse Genome Informatics Computational Sequence to Gene Associations |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Marc Feuermann, Huaiyu Mi, Pascale Gaudet, Dustin Ebert, Anushya Muruganujan, Paul Thomas |
Year: |
2010 |
|
Title: |
Annotation inferences using phylogenetic trees |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Database and National Center for Biotechnology Information |
Year: |
2000 |
Journal: |
Database Release |
Title: |
Entrez Gene Load |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics (MGI) and The National Center for Biotechnology Information (NCBI) |
Year: |
2010 |
Journal: |
Database Download |
Title: |
Consensus CDS project |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Group |
Year: |
2003 |
Journal: |
Database Procedure |
Title: |
Automatic Encodes (AutoE) Reference |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics |
Year: |
2010 |
Journal: |
Database Release |
Title: |
Protein Ontology Association Load. |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Bairoch A |
Year: |
1999 |
Journal: |
Database Release |
Title: |
SWISS-PROT Annotated protein sequence database |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2005 |
|
Title: |
Obtaining and loading genome assembly coordinates from NCBI annotations |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2009 |
Journal: |
Database Download |
Title: |
Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Gene 1.0 ST Array Platform |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2009 |
Journal: |
Database Download |
Title: |
Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Genome 430 2.0 Array Platform |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Allen Institute for Brain Science |
Year: |
2004 |
Journal: |
Allen Institute |
Title: |
Allen Brain Atlas: mouse riboprobes |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2005 |
|
Title: |
Obtaining and Loading Genome Assembly Coordinates from Ensembl Annotations |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Sadras T |
Year: |
2021 |
Journal: |
Mol Cell |
Title: |
Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. |
Volume: |
81 |
Issue: |
10 |
Pages: |
2094-2111.e9 |
|
•
•
•
•
•
|
UniProt Feature |
Begin: |
323 |
Description: |
Phosphotyrosine; by ZAP70 |
Type: |
modified residue |
End: |
323 |
|
•
•
•
•
•
|
UniProt Feature |
Begin: |
323 |
Description: |
Phosphotyrosine; by ZAP70 |
Type: |
modified residue |
End: |
323 |
|
•
•
•
•
•
|
Allele |
Name: |
zeta-chain (TCR) associated protein kinase; targeted mutation 3.1, Arthur Weiss |
Allele Type: |
Targeted |
Attribute String: |
Hypomorph |
|
•
•
•
•
•
|
Strain |
Attribute String: |
congenic, mutant strain, targeted mutation |
|
•
•
•
•
•
|
Publication |
First Author: |
Bekeredjian-Ding I |
Year: |
2008 |
Journal: |
J Immunol |
Title: |
TLR9-activating DNA up-regulates ZAP70 via sustained PKB induction in IgM+ B cells. |
Volume: |
181 |
Issue: |
12 |
Pages: |
8267-77 |
|
•
•
•
•
•
|
DO Term |
|
•
•
•
•
•
|
Publication |
First Author: |
Damen H |
Year: |
2022 |
Journal: |
Front Immunol |
Title: |
Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells. |
Volume: |
13 |
|
Pages: |
935367 |
|
•
•
•
•
•
|
Publication |
First Author: |
Liu X |
Year: |
2003 |
Journal: |
J Exp Med |
Title: |
Restricting Zap70 expression to CD4+CD8+ thymocytes reveals a T cell receptor-dependent proofreading mechanism controlling the completion of positive selection. |
Volume: |
197 |
Issue: |
3 |
Pages: |
363-73 |
|
•
•
•
•
•
|
Interaction Experiment |
Description: |
Usp9X Is Required for Lymphocyte Activation and Homeostasis through Its Control of ZAP70 Ubiquitination and PKC Kinase Activity. |
|
•
•
•
•
•
|
Allele |
Name: |
zeta-chain (TCR) associated protein kinase; endonuclease-mediated mutation 1, Shanghai Model Organisms Center |
Allele Type: |
Endonuclease-mediated |
Attribute String: |
Null/knockout |
|
•
•
•
•
•
|
Allele |
Name: |
transgene insertion 824, Shimon Sakaguchi |
Allele Type: |
Transgenic |
Attribute String: |
Inserted expressed sequence |
|
•
•
•
•
•
|
Publication |
First Author: |
Naik E |
Year: |
2016 |
Journal: |
J Immunol |
Title: |
Usp9X Is Required for Lymphocyte Activation and Homeostasis through Its Control of ZAP70 Ubiquitination and PKCβ Kinase Activity. |
Volume: |
196 |
Issue: |
8 |
Pages: |
3438-51 |
|
•
•
•
•
•
|
Strain |
Attribute String: |
coisogenic, mutant strain, endonuclease-mediated mutation |
|
•
•
•
•
•
|
Allele |
Name: |
zeta-chain (TCR) associated protein kinase; mutation 1, Bruce Beutler |
Allele Type: |
Chemically induced (ENU) |
|
|
•
•
•
•
•
|
Allele |
Name: |
transgene insertion 1, Andrew C Chan |
Allele Type: |
Transgenic |
Attribute String: |
Inserted expressed sequence |
|
•
•
•
•
•
|
Allele |
Name: |
transgene insertion 2, Andrew C Chan |
Allele Type: |
Transgenic |
Attribute String: |
Inserted expressed sequence |
|
•
•
•
•
•
|
Allele |
Name: |
transgene insertion 1, Andrew C Chan |
Allele Type: |
Transgenic |
Attribute String: |
Inserted expressed sequence |
|
•
•
•
•
•
|
Allele |
Name: |
spleen tyrosine kinase; targeted mutation 2.1, Friedemann Kiefer |
Allele Type: |
Targeted |
Attribute String: |
Inserted expressed sequence |
|
•
•
•
•
•
|
Genotype |
Symbol: |
Zap70/Zap70 |
Background: |
involves: C57BL/6J |
Zygosity: |
hm |
Has Mutant Allele: |
true |
|
•
•
•
•
•
|
Allele |
Name: |
zeta-chain (TCR) associated protein kinase; mutation 8, Bruce Beutler |
Allele Type: |
Chemically induced (ENU) |
Attribute String: |
Not Specified |
|
•
•
•
•
•
|
Strain |
Attribute String: |
mutant strain, coisogenic, chemically induced mutation |
|
•
•
•
•
•
|
Strain |
Attribute String: |
congenic, mutant strain, targeted mutation |
|
•
•
•
•
•
|
Publication |
First Author: |
Königsberger S |
Year: |
2012 |
Journal: |
EMBO J |
Title: |
Altered BCR signalling quality predisposes to autoimmune disease and a pre-diabetic state. |
Volume: |
31 |
Issue: |
15 |
Pages: |
3363-74 |
|
•
•
•
•
•
|
Genotype |
Symbol: |
Syk/Syk |
Background: |
B6.129-Syk |
Zygosity: |
hm |
Has Mutant Allele: |
true |
|
•
•
•
•
•
|
Genotype |
Symbol: |
Zap70/Zap70 |
Background: |
C57BL/6J-Zap70 |
Zygosity: |
hm |
Has Mutant Allele: |
true |
|
•
•
•
•
•
|
Genotype |
Symbol: |
Zap70/Zap70 Tg(Lck-ZAP70)824Saka/? |
Background: |
involves: 129P2/OlaHsd * BALB/c |
Zygosity: |
cx |
Has Mutant Allele: |
true |
|
•
•
•
•
•
|
HT Experiment |
|
Experiment Type: |
RNA-Seq |
Study Type: |
WT vs. Mutant |
Source: |
GEO |
|
•
•
•
•
•
|
Publication |
First Author: |
Dorn T |
Year: |
2007 |
Journal: |
Blood |
Title: |
RhoH is important for positive thymocyte selection and T-cell receptor signaling. |
Volume: |
109 |
Issue: |
6 |
Pages: |
2346-55 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lee JM |
Year: |
2004 |
Journal: |
J Immunol |
Title: |
IL-15Ralpha is a negative regulator of TCR-activated proliferation in CD4+ T cells. |
Volume: |
173 |
Issue: |
5 |
Pages: |
3155-64 |
|
•
•
•
•
•
|
Publication |
First Author: |
Cao W |
Year: |
2016 |
Journal: |
Nat Commun |
Title: |
CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation. |
Volume: |
7 |
|
Pages: |
11687 |
|
•
•
•
•
•
|
Publication |
First Author: |
Jiao A |
Year: |
2022 |
Journal: |
Sci Adv |
Title: |
DExD/H-box helicase 9 intrinsically controls CD8+ T cell-mediated antiviral response through noncanonical mechanisms. |
Volume: |
8 |
Issue: |
6 |
Pages: |
eabk2691 |
|
•
•
•
•
•
|
Publication |
First Author: |
McGargill MA |
Year: |
2005 |
Journal: |
J Immunol |
Title: |
Active Ca2+/calmodulin-dependent protein kinase II gamma B impairs positive selection of T cells by modulating TCR signaling. |
Volume: |
175 |
Issue: |
2 |
Pages: |
656-64 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hope JL |
Year: |
2023 |
Journal: |
Cell Rep |
Title: |
PSGL-1 attenuates early TCR signaling to suppress CD8(+) TÂ cell progenitor differentiation and elicit terminal CD8(+) TÂ cell exhaustion. |
Volume: |
42 |
Issue: |
5 |
Pages: |
112436 |
|
•
•
•
•
•
|
Publication |
First Author: |
Märklin M |
Year: |
2020 |
Journal: |
Cell Immunol |
Title: |
Genetic loss of NFAT2 (NFATc1) impairs B cell development of B1 and B2 B cells. |
Volume: |
349 |
|
Pages: |
104048 |
|
•
•
•
•
•
|
Publication |
First Author: |
Klammt C |
Year: |
2015 |
Journal: |
Nat Immunol |
Title: |
T cell receptor dwell times control the kinase activity of Zap70. |
Volume: |
16 |
Issue: |
9 |
Pages: |
961-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Round JL |
Year: |
2007 |
Journal: |
Nat Immunol |
Title: |
Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. |
Volume: |
8 |
Issue: |
2 |
Pages: |
154-61 |
|
•
•
•
•
•
|
Publication |
First Author: |
Courtney AH |
Year: |
2017 |
Journal: |
Mol Cell |
Title: |
A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45. |
Volume: |
67 |
Issue: |
3 |
Pages: |
498-511.e6 |
|
•
•
•
•
•
|
Publication |
First Author: |
Cheng J |
Year: |
2023 |
Journal: |
Cell Metab |
Title: |
Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8(+) TÂ cells in the tumor microenvironment. |
Volume: |
35 |
Issue: |
6 |
Pages: |
961-978.e10 |
|
•
•
•
•
•
|
Publication |
First Author: |
Königsberger S |
Year: |
2015 |
Journal: |
Eur J Immunol |
Title: |
Suboptimal B-cell antigen receptor signaling activity in vivo elicits germinal center counterselection mechanisms. |
Volume: |
45 |
Issue: |
2 |
Pages: |
603-11 |
|
•
•
•
•
•
|
Publication |
First Author: |
Liang W |
Year: |
2019 |
Journal: |
Mol Immunol |
Title: |
Ablation of core fucosylation attenuates the signal transduction via T cell receptor to suppress the T cell development. |
Volume: |
112 |
|
Pages: |
312-321 |
|
•
•
•
•
•
|
Publication |
First Author: |
Marquez ME |
Year: |
2005 |
Journal: |
J Immunol |
Title: |
CD8 T cell sensory adaptation dependent on TCR avidity for self-antigens. |
Volume: |
175 |
Issue: |
11 |
Pages: |
7388-97 |
|
•
•
•
•
•
|
Publication |
First Author: |
Kim EY |
Year: |
2004 |
Journal: |
J Immunol |
Title: |
Critical role of TNF receptor type-2 (p75) as a costimulator for IL-2 induction and T cell survival: a functional link to CD28. |
Volume: |
173 |
Issue: |
7 |
Pages: |
4500-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Leal-Sanchez J |
Year: |
2007 |
Journal: |
Cell Death Differ |
Title: |
Requirement for Daxx in mature T-cell proliferation and activation. |
Volume: |
14 |
Issue: |
4 |
Pages: |
795-806 |
|
•
•
•
•
•
|
Publication |
First Author: |
Bailey AR |
Year: |
2012 |
Journal: |
FASEB J |
Title: |
Aberrant T-lymphocyte development and function in mice overexpressing human soluble amyloid precursor protein-α: implications for autism. |
Volume: |
26 |
Issue: |
3 |
Pages: |
1040-51 |
|
•
•
•
•
•
|
Publication |
First Author: |
Troeger A |
Year: |
2013 |
Journal: |
J Biol Chem |
Title: |
A unique carboxyl-terminal insert domain in the hematopoietic-specific, GTPase-deficient Rho GTPase RhoH regulates post-translational processing. |
Volume: |
288 |
Issue: |
51 |
Pages: |
36451-62 |
|
•
•
•
•
•
|
Publication |
First Author: |
Armstrong AJ |
Year: |
2010 |
Journal: |
J Immunol |
Title: |
ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation. |
Volume: |
184 |
Issue: |
1 |
Pages: |
173-83 |
|
•
•
•
•
•
|
Publication |
First Author: |
Salojin K |
Year: |
1997 |
Journal: |
J Exp Med |
Title: |
Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice. |
Volume: |
186 |
Issue: |
6 |
Pages: |
887-97 |
|
•
•
•
•
•
|
Publication |
First Author: |
Haks MC |
Year: |
2002 |
Journal: |
J Exp Med |
Title: |
Contributions of the T cell receptor-associated CD3gamma-ITAM to thymocyte selection. |
Volume: |
196 |
Issue: |
1 |
Pages: |
1-13 |
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Publication |
First Author: |
Herling M |
Year: |
2006 |
Journal: |
Leukemia |
Title: |
TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state. |
Volume: |
20 |
Issue: |
2 |
Pages: |
280-5 |
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Publication |
First Author: |
Liu X |
Year: |
2005 |
Journal: |
J Immunol |
Title: |
Analyzing expression of perforin, Runx3, and Thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes. |
Volume: |
175 |
Issue: |
7 |
Pages: |
4465-74 |
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Publication |
First Author: |
Ambrogio C |
Year: |
2009 |
Journal: |
Cancer Res |
Title: |
NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. |
Volume: |
69 |
Issue: |
22 |
Pages: |
8611-9 |
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Publication |
First Author: |
Veronese A |
Year: |
2015 |
Journal: |
Leukemia |
Title: |
Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic lymphocytic leukemia. |
Volume: |
29 |
Issue: |
1 |
Pages: |
86-95 |
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Publication |
First Author: |
Law CL |
Year: |
1994 |
Journal: |
J Biol Chem |
Title: |
Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex. |
Volume: |
269 |
Issue: |
16 |
Pages: |
12310-9 |
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Publication |
First Author: |
Taniguchi T |
Year: |
1991 |
Journal: |
J Biol Chem |
Title: |
Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis. |
Volume: |
266 |
Issue: |
24 |
Pages: |
15790-6 |
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Protein Domain |
Type: |
Family |
Description: |
Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups []:Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis []. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction []. Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [].This entry represents the non-receptor tyrosine kinases SYK and ZAP-70 [, , ]:SYK is a positive effector of BCR-stimulated responses. It couples the B-cell antigen receptor (BCR) to the mobilisation of calcium ion, either through a phosphoinositide 3-kinase-dependent pathway (when not phosphorylated on tyrosines of the linker region), or through a phospholipase C-gamma-dependent pathway (when phosphorylated on Tyr-342 and Tyr-346). Therefore, the differential phosphorylation of Syk can determine the pathway by which BCR is coupled to the regulation of intracellular calcium ion [, ].ZAP70 plays a role in T-cell development and lymphocyte activation. It is essential for TCR-mediated IL-2 production. Isoform 1 of ZAP70 induces TCR-mediated signal transduction, isoform 2 does not [, ]. |
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Publication |
First Author: |
Chan AC |
Year: |
1992 |
Journal: |
Cell |
Title: |
ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. |
Volume: |
71 |
Issue: |
4 |
Pages: |
649-62 |
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Publication |
First Author: |
Reeve JL |
Year: |
2009 |
Journal: |
J Immunol |
Title: |
SLP-76 couples Syk to the osteoclast cytoskeleton. |
Volume: |
183 |
Issue: |
3 |
Pages: |
1804-12 |
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•
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Publication |
First Author: |
Ruzza P |
Year: |
2009 |
Journal: |
Expert Opin Ther Pat |
Title: |
Therapeutic prospect of Syk inhibitors. |
Volume: |
19 |
Issue: |
10 |
Pages: |
1361-76 |
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Publication |
First Author: |
Arpaia E |
Year: |
1994 |
Journal: |
Cell |
Title: |
Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. |
Volume: |
76 |
Issue: |
5 |
Pages: |
947-58 |
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
629
|
Fragment?: |
false |
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
618
|
Fragment?: |
false |
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
583
|
Fragment?: |
false |
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•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
629
|
Fragment?: |
false |
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•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
629
|
Fragment?: |
false |
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•
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