Genomes and Genes
zap 70 protein tyrosine kinase
Summary: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
- Xu W, Cao X, Miao K, Qiao C, Wu Y, Liu Q, et al. Serum thymidine kinase 1 concentration in Chinese patients with chronic lymphocytic leukemia and its correlation with other prognostic factors. Int J Hematol. 2009;90:205-211 pubmed publisher..75 pM, with a 87.8% specificity, a 63.6% sensitivity. It was showed that serum TK1 concentration could be a predictive marker of IGHV mutational status, and might be applied for the assessment of prognosis in patients with CLL. ..
- Ahmed S, Meklat F, Shahriar M, Zhang J, Mastulov S, Giannakouros T, et al. SEMG-1 expression in early stage chronic lymphocytic leukemia. Cytotherapy. 2009;11:238-44 pubmed publisher..SEMG-1 is expressed in nearly half of patients with early CLL and may be a target for further investigations into its use for immunotherapy of early CLL. ..
- Qiao G, Li Z, Minto A, Shia J, Yang L, Bao L, et al. Altered thymic selection by overexpressing cellular FLICE inhibitory protein in T cells causes lupus-like syndrome in a BALB/c but not C57BL/6 strain. Cell Death Differ. 2010;17:522-33 pubmed publisher..Therefore, we have identified c-FLIP(L) as a susceptibility factor under the influence of epistatic modifiers for the development of autoimmunity. ..
- Collins M, Bartelt R, Houtman J. T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells. Mol Immunol. 2010;47:1665-74 pubmed publisher..Collectively, these observations suggest that signaling pathways downstream of TCR activation are hard-wired to induce two separate periods of Pyk2 activation and actin cytoskeletal rearrangement. ..
- Podhorecka M, Klimek P, Kowal M, Chocholska S, Bojarska Junak A, Dmoszynska A. Assessment of peripheral blood and bone marrow cells apoptosis caused by purine analogues in patients with chronic lymphocytic leukemia in correlation with parameters of disease progression. Acta Haematol. 2010;123:171-8 pubmed publisher..The cells from ZAP-70-positive patients seem to enter apoptosis more readily than those from ZAP-70-negative patients; thus, ZAP-70-positive patients are more likely to benefit from treatment with purine analogues. ..
- Asquith D, Miller A, McInnes I, Liew F. Animal models of rheumatoid arthritis. Eur J Immunol. 2009;39:2040-4 pubmed publisher..Here, we describe these animal models and discuss their advantages and limitations. ..
- Vicente R, Adjali O, Jacquet C, Zimmermann V, Taylor N. Intrathymic transplantation of bone marrow-derived progenitors provides long-term thymopoiesis. Blood. 2010;115:1913-20 pubmed publisher..Thus, IT administration of BM progenitors results in the filling of an expanded precursor niche and may represent a strategy for enhancing T-cell differentiation in patients with SCID. ..
- Xu W, Li J, Shen Q, Wu Y, Yu H, Fan L. Expression level of lipoprotein lipase in Chinese patients with chronic lymphocytic leukemia and its correlation with other prognostic factors. Int J Lab Hematol. 2009;31:552-9 pubmed publisher..404, P = 0.002). It was showed that LPL expression correlates with IgVH mutational status and other clinical or laboratory prognostic factors, and might be applied for the assessment of prognosis in patients with CLL. ..
- Ambrogio C, Martinengo C, Voena C, Tondat F, Riera L, di Celle P, et al. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. Cancer Res. 2009;69:8611-9 pubmed publisher..Thus, our data reveal that oncogene-deregulated tyrosine kinase activity controls the expression of molecules that determine T-cell identity and signaling. ..
- Purbhoo M, Liu H, Oddos S, Owen D, Neil M, Pageon S, et al. Dynamics of subsynaptic vesicles and surface microclusters at the immunological synapse. Sci Signal. 2010;3:ra36 pubmed publisher..Together, these data show that the movement of LAT-containing vesicles is linked to the organization of protein microclusters and suggest an important role for vesicular LAT in the SLP-76 signalosome...
- Jain N, Lamanna N. Incorporating prognostic information into treatment decisions in chronic lymphocytic leukemia. Curr Oncol Rep. 2009;11:353-9 pubmed..To date, no study has shown a benefit from early cytotoxic therapy for any subgroup of patients with chronic lymphocytic leukemia. ..
- Quintero Rivera F, Nooraie F, Rao P. Frequency of 5'IGH deletions in B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet. 2009;190:33-9 pubmed publisher..Longitudinal studies are warranted, to determine when in the disease progression this abnormality is acquired, as a potential early marker, and its impact on the natural history of CLL. ..
- Zum Büschenfelde C, Wagner M, Lutzny G, Oelsner M, Feuerstacke Y, Decker T, et al. Recruitment of PKC-betaII to lipid rafts mediates apoptosis-resistance in chronic lymphocytic leukemia expressing ZAP-70. Leukemia. 2010;24:141-52 pubmed publisher..We provide evidence that this compound is highly active in leukemic cells and augments the cytotoxic effects of standard chemotherapeutic drugs. ..
- García Bernal D, Parmo Cabañas M, Dios Esponera A, Samaniego R, Hernán P de la Ossa D, Teixido J. Chemokine-induced Zap70 kinase-mediated dissociation of the Vav1-talin complex activates alpha4beta1 integrin for T cell adhesion. Immunity. 2009;31:953-64 pubmed publisher..Our data suggest that Vav1 might function as a repressive adaptor of talin that must dissociate from alpha4beta1-talin complexes for efficient integrin activation. ..
- COLGAN J, Hankel I. Signaling pathways critical for allergic airway inflammation. Curr Opin Allergy Clin Immunol. 2010;10:42-7 pubmed publisher..The knowledge acquired may lead to novel approaches for suppressing allergic inflammation. ..
- Burger J, Quiroga M, Hartmann E, Bürkle A, Wierda W, Keating M, et al. High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation. Blood. 2009;113:3050-8 pubmed publisher..Through these chemokines, CLL cells can recruit accessory cells and thereby actively create a supportive microenvironment. ..
- Podhorecka M, Halicka D, Klimek P, Kowal M, Chocholska S, Dmoszynska A. Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010;89:1115-24 pubmed publisher..One of the mechanisms of simvastatin action is inducing DNA damage that ultimately leads to apoptosis. ..
- Varma R, Campi G, Yokosuka T, Saito T, Dustin M. T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity. 2006;25:117-27 pubmed..Our studies reveal a role for F-actin in TCR signaling beyond microcluster formation. ..
- Clarke R, Thiemann S, Refaeli Y, Werlen G, Potter T. A new function for LAT and CD8 during CD8-mediated apoptosis that is independent of TCR signal transduction. Eur J Immunol. 2009;39:1619-31 pubmed publisher..Our results identify novel functions for both CD8 and LAT that are independent of TCR signal transduction and suggest a mechanism for signal transduction leading to apoptosis upon CD8 crosslinking. ..
- Picard C, Dogniaux S, Chemin K, Maciorowski Z, Lim A, Mazerolles F, et al. Hypomorphic mutation of ZAP70 in human results in a late onset immunodeficiency and no autoimmunity. Eur J Immunol. 2009;39:1966-76 pubmed publisher..This report extends the phenotype spectrum of ZAP70 deficiency with a residual function of ZAP70. ..
- Sahlander K, Larsson K, Palmberg L. Increased serum levels of soluble ST2 in birch pollen atopics and individuals working in laboratory animal facilities. J Occup Environ Med. 2010;52:214-8 pubmed publisher..Increased CD14 expression found in LA workers is most likely a response to non-allergic agent exposure whereas ST2 seems to react to acute allergen exposure and to non-allergic stimuli as pathogen-associated molecular patterns. ..
- Konoplev S, Fritsche H, O Brien S, Wierda W, Keating M, Gornet T, et al. High serum thymidine kinase 1 level predicts poorer survival in patients with chronic lymphocytic leukemia. Am J Clin Pathol. 2010;134:472-7 pubmed publisher..We suggest that serum TK1 levels analyzed using this convenient chemiluminescence assay may be useful in the risk assessment of patients with CLL. ..
- Srisurapanon S, Sukwit S, Chuenchitra T, Santiwattanakul S. ZAP-70 positive cells in treated and untreated HIV-1 infected patients. Southeast Asian J Trop Med Public Health. 2010;41:146-52 pubmed..Elevated MFI levels of ZAP-70 molecules in CD4+ cells in HIV infected patients may be associated with an inability to further activate T-cells. ..
- Motiwala T, Datta J, Kutay H, Roy S, Jacob S. Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib. J Cell Biochem. 2010;110:846-56 pubmed publisher..These results have revealed the physiological importance of PTPROt in regulating B-cell receptor signaling at Lyn kinase. Further, ectopic expression of PTPROt also sensitized the cells to the VEGF-R inhibitor Pazopanib. ..
- Morabito F, Cutrona G, Gentile M, Matis S, Todoerti K, Colombo M, et al. Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia. Br J Haematol. 2009;146:44-53 pubmed publisher..8, 95% confidence interval (CI) 2.4-5.8] and high-risk group (HR = 8.0, 95% CI 3.9-16.2). Specific transcriptional patterns were significantly associated with risk groups. ..
- Wang H, Kadlecek T, Au Yeung B, Goodfellow H, Hsu L, Freedman T, et al. ZAP-70: an essential kinase in T-cell signaling. Cold Spring Harb Perspect Biol. 2010;2:a002279 pubmed publisher..Here we review the structure of ZAP-70, its regulation, its role in development and in disease. We also describe a model experimental system in which ZAP-70 function can be interrupted by a small chemical inhibitor. ..
- Lobo P, Schlegal K, Vengal J, Okusa M, Pei H. Naturally occurring IgM anti-leukocyte autoantibodies inhibit T-cell activation and chemotaxis. J Clin Immunol. 2010;30 Suppl 1:S31-6 pubmed publisher..The innate anti-inflammatory mechanism of IgM-ALA can be exploited by using purified normal IgM to inhibit inflammatory states or by a vaccine approach to increase in vivo production of IgM-ALA (e.g., prior to a transplant). ..
- Kelly E, Wang L, Ivashkiv L. Calcium-activated pathways and oxidative burst mediate zymosan-induced signaling and IL-10 production in human macrophages. J Immunol. 2010;184:5545-52 pubmed publisher..These observations identify a new calcium-mediated signaling pathway activated by zymosan and link this pathway to both inflammatory and anti-inflammatory responses in macrophages. ..
- Laszlo D, Andreola G, Rigacci L, Fabbri A, Rabascio C, Mancuso P, et al. Rituximab and subcutaneous 2-chloro-2'-deoxyadenosine combination treatment for patients with Waldenstrom macroglobulinemia: clinical and biologic results of a phase II multicenter study. J Clin Oncol. 2010;28:2233-8 pubmed publisher..The pharmacogenomic analysis associated with the study suggests hCNT1 might be beneficial in predicting clinical response to such a combination treatment. ..
- Xu W, Shen Q, Yu H, Qiao C, Wu Y, Liu Q, et al. [Lipoprotein lipase and serum thymidine kinase level in chronic lymphocytic leukemia and their correlations with other prognostic factors]. Zhonghua Xue Ye Xue Za Zhi. 2009;30:8-12 pubmed..LPL expression and serum TK1 levels significantly correlate with other CLL prognostic factors and could be predictive markers for IgVH mutation status. LPL and serum TK1 might be applied to the assessment of prognosis in CLL patients. ..
- Pido Lopez J, Jeffrey P, Wang Y, Seidl T, Babaahmady K, Vaughan R, et al. The effect of allogeneic in vitro stimulation and in vivo immunization on memory CD4(+) T-cell APOBEC3G expression and HIV-1 infectivity. Eur J Immunol. 2009;39:1956-65 pubmed publisher..The results suggest that alloimmunization offers an alternative or complementary strategy in inducing an innate anti-viral factor that inhibits HIV-1 infection. ..
- Wang X, Barnes P, Dobos Elder K, Townsend J, Chung Y, Shams H, et al. ESAT-6 inhibits production of IFN-gamma by Mycobacterium tuberculosis-responsive human T cells. J Immunol. 2009;182:3668-77 pubmed publisher..We conclude that ESAT-6 directly inhibits human T cell responses to mycobacterial Ags by affecting TCR signaling pathways downstream of ZAP70...
- Chantepie S, Vaur D, Grunau C, Salaün V, Briand M, Parienti J, et al. ZAP-70 intron1 DNA methylation status: determination by pyrosequencing in B chronic lymphocytic leukemia. Leuk Res. 2010;34:800-8 pubmed publisher..0001), IgHv mutation status (n=106, p<.0001), time to treatment (p<.0001), and overall survival (p=.0014). Pyrosequencing of ZAP-70 provides a good alternative to flow cytometry. ..
- Mcelligott A, Maginn E, Greene L, McGuckin S, Hayat A, Browne P, et al. The novel tubulin-targeting agent pyrrolo-1,5-benzoxazepine-15 induces apoptosis in poor prognostic subgroups of chronic lymphocytic leukemia. Cancer Res. 2009;69:8366-75 pubmed publisher..The need for novel treatments is acute in CLL, especially for the subgroup of patients with poor clinical outcome and drug-resistant disease. This study identifies a novel agent with significant clinical potential. ..
- ..Mutations in the adaptor molecule LAT can lead to autoimmunity. In this issue of Immunity, Mingueneau et al. (2009) describe how this may not be a failure of central tolerance. ..
- Leavenworth J, Pauza M. Engagement of transgenic Ly49A inhibits mouse CD4 cell activation by disrupting T cell receptor, but not CD28, signaling. Cell Immunol. 2009;257:88-96 pubmed publisher..These results suggest that when considering its use as an immunotherapy, the potency of inhibitory receptors such as Ly49A may be further improved by pairing them with costimulatory blockade. ..
- del Giudice I, Chiaretti S, Tavolaro S, De Propris M, Maggio R, Mancini F, et al. Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases. Blood. 2009;114:638-46 pubmed publisher..The peculiar gene profile suggests that BCR signaling may play an important role in this scenario as the most significant feature of the leukemic clone in regression. ..
- Layton T, Stalens C, Gunderson F, Goodison S, Silletti S. Syk tyrosine kinase acts as a pancreatic adenocarcinoma tumor suppressor by regulating cellular growth and invasion. Am J Pathol. 2009;175:2625-36 pubmed publisher..This study demonstrates a prominent role for syk in regulating the differentiation state and invasive phenotype of PDAC cells. ..
- Das Roy L, Pathangey L, Tinder T, Schettini J, Gruber H, Mukherjee P. Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis. Breast Cancer Res. 2009;11:R56 pubmed publisher..The data clearly has important clinical implications for patients diagnosed with metastatic breast cancer, especially with regards to the prognosis and treatment options. ..
- Tribulatti M, Cattaneo V, Hellman U, Mucci J, Campetella O. Galectin-8 provides costimulatory and proliferative signals to T lymphocytes. J Leukoc Biol. 2009;86:371-80 pubmed publisher..Taken together, our findings support a distinctive role for locally produced Gal-8 as an enhancer of otherwise borderline immune responses and also suggest that Gal-8 might fuel the reactivity at inflammatory foci. ..
- Del Poeta G, Del Principe M, Maurillo L, Rossi F, Buccisano F, Ammatuna E, et al. Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia. Leuk Lymphoma. 2010;51:95-106 pubmed publisher..03) was confirmed within ZAP-70 negative patients. Bcl-2 and CD71 can be considered as interesting progression indicators, which should be validated in an independent cohort of patients, to take timely therapeutic decisions in CLL. ..
- Choudhuri K, Parker M, Milicic A, Cole D, Shaw M, Sewell A, et al. Peptide-major histocompatibility complex dimensions control proximal kinase-phosphatase balance during T cell activation. J Biol Chem. 2009;284:26096-105 pubmed publisher..These findings demonstrate that T cell antigen recognition is strongly dependent on pMHC size and are consistent with models of TCR triggering requiring segregation or mechanical pulling of the TCR. ..
- Ziemba S, Menard S, McCabe M, Rosenspire A. T-cell receptor signaling is mediated by transient Lck activity, which is inhibited by inorganic mercury. FASEB J. 2009;23:1663-71 pubmed publisher..Thus, Hg(2+) inhibits a critical activating role played by Lck Y192 during the most proximal events of the TCR-induced cell signaling. ..
- Srivastava S, Di L, Zhdanova O, Li Z, Vardhana S, Wan Q, et al. The class II phosphatidylinositol 3 kinase C2beta is required for the activation of the K+ channel KCa3.1 and CD4 T-cells. Mol Biol Cell. 2009;20:3783-91 pubmed publisher..This is the first demonstration that a class II PI3K plays a critical role in T-cell activation. ..
- Visone R, Rassenti L, Veronese A, Taccioli C, Costinean S, Aguda B, et al. Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood. 2009;114:3872-9 pubmed publisher..Thus, the use of the microRNA-based classifications may yield clinically useful biomarkers of tumor behavior in CLL. ..
- Vroblova V, Vrbacky F, Hrudkova M, Jankovicova K, Schmitzova D, Maly J, et al. Significant change in ZAP-70 expression during the course of chronic lymphocytic leukemia. Eur J Haematol. 2010;84:513-7 pubmed publisher..Based on our pilot results, repeated assessment of ZAP-70 expression might be especially useful at the time of progression or relapse in patients who were initially ZAP-70-negative. ..