Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Visualization by autoradiography of specific IgE binding in crossed radioimmunoelectrophoresis (CRIE) and other 125I-immunoautoradiography (IAR) techniques is done in two different ways; either by traditional direct autoradiography (D-ARG), where the film is exposed to the 125I-anti-IgE incubated sample at room temperature, or by indirect autoradiography (ID-ARG), applying intensifying screen, low-temperature exposure and, eventually, pre-exposure. This study confirmed that D-ARG provided the benefits of simplicity and better image resolution with the disadvantage of prolonged exposure periods. ID-ARG reduced the exposures needed to produce film image densities of 0.01 and 0.1 A540 nm (i.e. autoradiographic sensitivity (AR sigma) and autoradiographic speed (ARs] to 1/18 and 1/55 respectively of the corresponding exposures in D-ARG. The lowest detection limits for 125I in 24 h were 1.2 cpm mm-2 with the indirect and 6.8 cpm mm-2 with the direct systems investigated. The major drawbacks of ID-ARG were inferior image resolution and higher background levels, especially when pre-exposure was included.
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PMID:Comparative studies on tree pollen allergens. XII. Evaluation of direct and indirect autoradiography systems for 125I in crossed radioimmunoelectrophoresis and other immunoautoradiographic techniques. 368 89

During a 7-year period, venom immunotherapy has been stopped in 57 patients because of a fall in IgE antibody titers to insignificant levels (RAST less than 10% STD). All patients had a history of venom anaphylaxis and elevated venom-specific IgE before therapy. Maintenance doses of 50 micrograms were administered every 4 to 6 weeks; 30 patients received yellow jacket venom, and 16 patients received honeybee venom only. Therapy was stopped after treatment from 1 to 8 years (mean 2.8 years). Repeat skin tests demonstrated an average two-log decrease in sensitivity; 35 of 55 tests remained positive at venom concentrations of less than or equal to 0.1 micrograms/ml. There were 55 re-stings in 24 patients, occurring from 3 months to 5 years after cessation of therapy, resulting in three systemic reactions. One patient, previously treated with bee venom, reacted to a yellow jacket sting. These re-sting reactors also had tolerated several other stings after therapy was stopped. Thus, the two actual reactions represent a "failure" rate of 8% per patient and 4% per sting, compared to reaction rates of 27% and 17% in patients who stopped therapy without physician advice. These data suggest that this criterion may be reliable for stopping therapy. However, subsequent tolerated re-stings may require continued patient evaluation.
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PMID:Evaluation of decline in serum venom-specific IgE as a criterion for stopping venom immunotherapy. 371 49

With the aid of a specific rabbit antibody preparation to purified monoclonal murine IgE, two plaque-forming cell (PFC) assays have been developed for the detection and enumeration of mouse IgE-secreting cells. The first assay, utilizing protein A-coated sheep red cells (protein A-SRC), detected antibody-secreting cells on the basis of the class of the secreted Ig irrespective of antigen specificity. With this assay, 30% of the class of the viable cells of two distinct IgE-secreting hybridoma cell lines were scored as PFC. Under these conditions, plaques were not obtained with IgG1 or IgG2a-secreting hybridoma cells. The second PFC assay, which utilized SRC coated with ovalbumin (OA-SRC), enumerated cells secreting anti-OA IgE antibodies. Similar kinetic patterns were observed for the cellular (IgE PFC/spleen) and humoral (IgE serum levels) responses of (C57BL/6 x DBA/2)F1 mice following immunization with 10 micrograms of OA adsorbed to 1 mg of A1(OH)3. Thus, it is concluded that the reverse plaque assay detecting all IgE-secreting cells, as well as the antigen-specific IgE PFC assay, can be used for the quantitation of IgE responses at the cellular level.
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PMID:The enumeration of mouse IgE-secreting cells using plaque-forming cell assays. 616 50

Vav is a recently described proto-oncogene expressed only in hematopoietic cells which contains an SH2 and two SH3 domains and shares homology with the Dbl GDP-GTP exchange factor and BCR. p95Vav is phosphorylated on tyrosine residues in response to stimulation of the T cell antigen receptor, cross-linking of IgE or IgM receptors and stimulation of immature hematopoietic cells by Steel factor. Monoclonal antibodies to human Vav were generated and used to examine the events which regulate tyrosine phosphorylation of p95Vav in myeloid cells. In the factor-dependent MO7e cell line, p95Vav was rapidly phosphorylated on tyrosine residues in a dose- and time-dependent manner by GM-CSF, IL-3 and Steel factor. Introduction of the BCR/ABL oncogene into this cell line resulted in factor-independent proliferation and constitutive phosphorylation of p95Vav. Tyrosine phosphorylation of p95Vav was also substantially increased by treatment of cytokine-deprived cells with the tyrosine phosphatase inhibitor sodium vanadate. Since many of the cytokines known to induce tyrosine phosphorylation of p95Vav are also known to activate JAK family tyrosine kinases, we looked for an interaction of p95Vav with JAK kinases. p95Vav co-precipitated with JAK2 in MO7e cells stimulated with GM-CSF, but not in unstimulated cells. Also, JAK2 was found to be constitutively associated with p95Vav in vivo when expressed at high levels in insect cells using baculovirus vectors. A fusion protein consisting of glutathione-S-transferase and the SH2 domain of p95Vav (GST-Vav-SH2) precipitated JAK2, suggesting that this interaction is mediated by the SH2 domain of p95Vav.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL. 749 7

The cytokines interleukin (IL) 4 and IL-13 induce many of the same biological responses, including class switching to IgE and induction of major histocompatibility complex class II antigens and CD23 on human B cells. It has recently been shown that IL-4 induces the tyrosine phosphorylation of a 170-kDa protein, a substrate called 4PS, and of the Janus kinase (JAK) family members JAK1 and JAK3. Because IL-13 has many functional effects similar to those of IL-4, we compared the ability of IL-4 and IL-13 to activate these signaling molecules in the human multifactor-dependent cell line TF-1. In this report we demonstrate that both IL-4 and IL-13 induced the tyrosine phosphorylation of 4PS and JAK1. Interestingly, although IL-4 induced the tyrosine phosphorylation of JAK3, we did not detect JAK3 phosphorylation in response to IL-13. These data suggest that IL-4 and IL-13 signal in similar ways via the activation of JAK1 and 4PS. However, our data further indicate that there are significant differences because IL-13 does not activate JAK3.
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PMID:Similarities and differences in signal transduction by interleukin 4 and interleukin 13: analysis of Janus kinase activation. 754

Cross-linking of the high-affinity IgE receptor (Fc epsilon RI) on mast cells induces rapid phosphorylation on serine, threonine, and tyrosine residues and increases the enzymatic activity, of a Tec subfamily tyrosine kinase, Itk/Tsk/Emt (Emt). The pleckstrin homology domain of Emt at its amino-terminal interacts directly with multiple isoforms of protein kinase C (PKC) in vitro. In addition, a portion of Emt is physically associated with multiple isoforms of PKC in intact mast cells. PKC phosphorylates a bacterial fusion protein containing the pleckstrin homology domain of Emt in vitro. Coexpression of Emt in COS-7 cells with Ca(2+)-dependent PKC isoforms (alpha, beta I, or beta II) induces an enhancement in tyrosine phosphorylation of Emt. In vivo inhibition of PKC expression or activity attenuates tyrosine phosphorylation and enzymatic activity of Emt induced upon Fc epsilon RI cross-linking. These data collectively suggest that PKC phosphorylates Emt and activates its autophosphorylating activity. Alternatively, PKC could activate another tyrosine kinase that phosphorylates Emt, or PKC-mediated phosphorylation of Emt may render it a target for another tyrosine kinase. In any case, PKC appears to play a major role in the activation of Emt induced upon Fc epsilon RI cross-linking.
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PMID:Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on Fc epsilon RI cross-linking on mast cells. 756 Oct 53

Mice homozygous for a disruption at the Lyn locus display abnormalities associated with the B lymphocyte lineage and in mast cell function. Despite reduced numbers of recirculating B lymphocytes, Lyn-/- mice are immunoglobulin M (IgM) hyperglobulinemic. Immune responses to T-independent and T-dependent antigens are affected. Lyn-/- mice fail to mediate an allergic response to IgE cross-linking, indicating that activation of LYN plays an indispensable role in Fc epsilon RI signaling. Lyn-/- mice have circulating autoreactive antibodies, and many show severe glomerulonephritis caused by the deposition of IgG immune complexes in the kidney, a pathology reminiscent of systemic lupus erythematosus. Collectively, these results implicate LYN as having an indispensable role in immunoglobulin-mediated signaling, particularly in establishing B cell tolerance.
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PMID:Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. 758 47

The focal adhesion kinase, pp125FAK, is a novel non-receptor protein tyrosine kinase expressed in different cells including mast cells. Here we report that a 77-kDa protein associates with pp125FAK in the mast cell analog, rat basophilic leukemia (RBL-2H3) cells. When pp125FAK immunoprecipitates were subjected to an in vitro kinase assay, there was prominent phosphorylation on tyrosine of pp125FAK and of a 77-kDa protein. By V8 protease digestion mapping and by immunoblotting with two different anti-pp125FAK antibodies, the 77-kDa protein was distinct from pp125FAK. This Fak Associated Protein or FAP was detected in RBL-2H3 cells but not in fibroblasts. The aggregation of the high affinity IgE receptor, Fc epsilon RI, induced the in vivo tyrosine phosphorylation of FAP. However, there was a marked decrease in the in vitro phosphorylation of FAP in the immunoprecipitates from Fc epsilon RI aggregated cells. Both of these Fc epsilon RI-mediated effects were enhanced by cell adhesion. There was strong association of FAP with non-tyrosine-phosphorylated pp125FAK. Thus this interaction does not appear to be mediated by the Src homology 2 domain. Together the data indicate that FAP associates with pp125FAK and suggest that FAP may play a role in Fc epsilon RI signaling.
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PMID:A 77-kDa protein associates with pp125FAK in mast cells and becomes tyrosine-phosphorylated by high affinity IgE receptor aggregation. 774 83

High affinity IgE receptors (alpha beta gamma 2) mediate the activation of the non-receptor tyrosine kinases Lyn and Syk. Here we show that the antioxidant drug N-acetyl-L-cysteine (NAC) inhibits antigen-mediated Syk activation whereas Lyn activation and phosphorylation of beta and gamma is maintained. Furthermore, NAC inhibits antigen-mediated calcium mobilization and exocytosis in a dose-dependent manner, but does not inhibit ionomycin-induced exocytosis. These data support a model in which the activation of Lyn is responsible for receptor phosphorylation and precedes the activation of Syk. The inhibition of Syk activation by NAC may be relevant to B and T cell antigen receptors, which are also linked to Syk/ZAP70 tyrosine kinases.
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PMID:N-acetyl-L-cysteine inhibits antigen-mediated Syk, but not Lyn tyrosine kinase activation in mast cells. 800 75

Despite the recent advances in knowledge of the molecular mechanism by which interleukin-4 (IL-4) induces IgE production, little is known about the signal transduction pathway that leads to this event. This study investigated the signal transduction mechanism responsible for IL-4-induced expression of germ-line C epsilon transcripts with use of a human Burkitt lymphoma B-cell line, DND39, which is known to express germ-line C epsilon transcripts in response to IL-4. On stimulation with IL-4, the generation of inositol triphosphate was observed in the cells. In addition, this generation was associated with activation of phospholipase C-gamma 1 (PLC-gamma 1). Although herbimycin A, a potent inhibitor of tryosine kinase, inhibited IL-4-induced activation of PLC-gamma 1 and generation of inositol triphosphate, direct phosphorylation of PCL-gamma 1 was not determined. Nevertheless, IL-4 stimulation could induce activation of FYN but not LYN kinase, suggesting that additional molecule(s) might link FYN kinase to PLC-gamma 1. Interestingly, herbimycin A almost completely inhibited IL-4-induced expression of germ-line C epsilon transcripts when present during the entire culture period. These results indicate that the induction of germ-line C epsilon transcripts in IL-4-stimulated DND39 cells is essentially dependent on the activation of tyrosine kinase, possibly FYN kinase.
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PMID:Possible role of tyrosine kinase activity in interleukin 4-induced expression of germ-line C epsilon transcripts in a human Burkitt lymphoma B-cell line, DND39. 808 70


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