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)

HSB-2 is a cell line derived from a patient who had T-cell acute lymphoblastic leukemia (T-cell ALL) with a t(1;7)(p34;q34). We used a genomic probe from the T-cell receptor beta (TCR beta) locus (7q34) to identify DNA rearrangements in HSB-2. Two rearranged BglII DNA fragments were cloned, and one of these clones was shown to contain the translocation breakpoint on the derivative chromosome I [der(I)]. We used a probe derived from this clone to isolate an unrearranged phage clone encompassing the breakpoint at Ip34. The restriction map of this clone was compared to the published maps of known protooncogenes located at Ip32-34. By restriction mapping, Southern blot analysis, and DNA sequencing we showed that the translocation breakpoint on chromosome I is located within the first intron of the LCK gene. The LCK gene codes for p56lck, a member of the SRC family of cytoplasmic tyrosine protein kinases. There are two classes of LCK transcripts (type I and type II), each expressed from a distinct promoter, and each having a unique 5' untranslated region (UTR); the protein coding regions of the two classes are identical. The breakpoint in the t(1;7) separates the two LCK promoters and juxtaposes the constant region of the TCR beta locus with the proximal promoter and with the protein-coding region of the LCK gene on the der(I) chromosome.
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PMID:The LCK gene is involved in the t(1;7)(p34;q34) in the T-cell acute lymphoblastic leukemia derived cell line, HSB-2. 166 80

In patients with B-cellular chronic lympholeukemia the blood lymphocyte rosette formation with sheep and mouse red cells (SRC and MRS) and estimation of the ratio between SRC- and MRC-receptor carrying lymphocyte subpopulations helps assess the intactness of T-cellular function, disease phase (remission or exacerbation) and prognosis, and patient's sensitivity to chemotherapy.
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PMID:[The phenotype of lymphocytes in B-type chronic lymphoid leukosis]. 169 65

The MARCKS (myristylated alanine-rich C-kinase substrate) protein is an abundant calmodulin-binding protein that is a major and specific endogenous substrate of protein kinase C (PKC). Stimulation of cells with phorbol esters or other activators of PKC has been shown previously to result in rapid phosphorylation of MARCKS proteins and redistribution of these myristylated C-kinase substrates from membrane to cytosol. Here we show that NIH3T3 murine fibroblasts transformed by p21-HA-C-RAS or pp60-V-SRC oncoproteins have markedly reduced levels of p68-MARCKS and that most of the remaining MARCKS protein is found in the cytosol. 3T3 cells containing a nontransforming oncoprotein p26-BCL2, in contrast, exhibited normal levels and distribution of p68-MARCKS. When taken together with recent evidence that MARCKS proteins are involved in regulating organization of the membrane cytoskeleton, our findings suggest that oncoprotein-mediated alterations in MARCKS protein levels and subcellular distribution may contribute to the development or maintenance of the transformed phenotype.
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PMID:Transformed 3T3 cells have reduced levels and altered subcellular distribution of the major PKC substrate protein MARCKS. 183 87

Leflunomide has been shown to be very effective in preventing and curing several autoimmune animal diseases. Further, this agent is as effective as cyclosporin A in preventing the rejection of skin and kidney transplants in rats. Preliminary results from patients suffering from severe cases of rheumatoid arthritis demonstrated that clinical and immunological parameters could be improved with leflunomide therapy. Mode of action studies revealed that this substance antagonizes the proliferation inducing activity of several cytokines and is cytostatic for certain cell types. In this light, we could show that tyrosine phosphorylation of the RR-SRC peptide substrate and the autophosphorylation of the epidermal growth factor (EGF) receptor were, dose dependently, inhibited by leflunomide. EGF activates the intrinsic tyrosine kinase of its receptor, which stimulates the phosphorylation of a variety of peptides, the amino acid residue in all cases is tyrosine. These results indicate that much of leflunomide's activity could be due to the inhibition of tyrosine-kinase(s), which is an important general mechanism for the proliferation of various cell types. Thus, leflunomide, which is effective against autoimmune diseases and reactions leading to graft rejection, would seem to have a mode of action separating it from known immunosuppressive drugs.
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PMID:Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection. 205 54

The effect of a synthetic peptide, corresponding to a sequence of HIV-1 p24 protein (amino acids 218-237), on in vitro immune responses was studied. The peptide inhibited in a dose-dependent manner the induction of an anti-SRC antibody response and of a PPD-specific proliferative response of human PBL. On the other hand, PHA-induced proliferation of human PBL and PPD-induced proliferation of a PPD-specific human T-cell line were not modified by comparable amounts of the peptide. These results suggest that structures from a protein (p24), present in the serum throughout the course of HIV infection, are able to interfere with the inductive stages of specific immune responses. These findings may help to unravel some of the pathogenic mechanisms of AIDS and may contribute to the development of vaccine strategies.
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PMID:Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV. 211 80

The classic problem of stimulus-response (S-R) compatibility (SRC) is addressed. A cognitive model is proposed that views the stimulus and response sets in S-R ensembles as categories with dimensions that may or may not overlap. If they do overlap, the task may be compatible or incompatible, depending on the assigned S-R mapping. If they do not overlap, the task is noncompatible regardless of the assigned mapping. The overlapping dimensions may be relevant or not. The model provides a systematic account of SRC effects, a taxonomy of simple performance tasks that were hitherto thought to be unrelated, and suggestive parallels between these tasks and the experimental paradigms that have traditionally been used to study attentional, controlled, and automatic processes.
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PMID:Dimensional overlap: cognitive basis for stimulus-response compatibility--a model and taxonomy. 218 25

From the studies presented above, it is obvious that fatty acylation is a common modification among proteins involved in cellular regulatory pathways, and in certain cases mutational analyses have demonstrated the importance of covalent fatty acids in the functioning of these proteins. Indeed, certain properties provided by fatty acylation make it an attractive modification for regulatory proteins that might interact with many different substrates, particularly those found at or near the plasma membrane/cytosol interface. In the case of intracellular fatty acylated proteins, the fatty acyl moiety allows tight binding to the plasma membrane without the need for cotranslational insertion through the bilayer. For example, consider the tight, salt-resistant interaction of myristoylated SRC with the membrane, whereas its nonmyristoylated counterpart is completely soluble. Likewise for the RAS proteins, which associate weakly with the membrane in the absence of fatty acylation, while palmitoylation increases their affinity for the plasma membrane and their biological activity. Fatty acylation also permits reversible membrane association in some cases, particularly for several myristoylated proteins, thus conferring plasticity on their interactions with various signaling pathway components. Finally, although this has not been demonstrated, it is conceivable that covalent fatty acid may allow for rapid mobility of proteins within the membrane. Several questions remain to be answered concerning requirements for fatty acylation by regulatory proteins. The identity of the putative SRC "receptor" will provide important clues as to the pathways in which normal SRC functions, as well as into the process of transformation by oncogenic tyrosine kinases. The possibility that other fatty acylated proteins associate with the plasma membrane in an analogous manner also needs to be investigated. An intriguing observation that can be made from the information presented here is that at least three different families of proteins involved in growth factor signaling pathways encode both acylated and nonacylated members, suggesting that selective fatty acylation may provide a means of determining the specificity of their interactions with other regulatory molecules. Further studies of fatty acylated proteins should yield important information concerning the regulation of intracellular signaling pathways utilized during growth and differentiation.
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PMID:Fatty acylated proteins as components of intracellular signaling pathways. 218 94

A novel member of the SRC tyrosine kinase gene family was recently isolated and characterized (Hao et al., 1989). This FES/FPS-related gene, named FER, lacks the transmembrane and extracellular domains which characterize tyrosine kinases with receptor function. Expression of FER in a wide range of cell types indicates a general role in intracellular signalling or differentiation processes. We have now mapped FER to chromosome 5q14----q23 using in situ hybridization techniques and suggest a more precise location within bands 5q21----q22. This region lies adjacent to a complex domain of growth factors and receptors, many involved in regulation of haematopoiesis. FER maps within a critical segment frequently deleted from chromosome 5 in patients with acute myeloid leukemia or myelodysplastic syndromes and was shown to be deleted in two such patients. It also maps close to the familial polyposis coli locus at 5q22.
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PMID:The human tyrosine kinase gene (FER) maps to chromosome 5 and is deleted in myeloid leukemias with a del(5q). 220 86

We evaluated the effect of various immunosuppressive drugs in the SRC assay. We chose the most appropriate day to obtain the results of the SRC assay using the MBT-2 tumor. MBT-2 tumor-bearing mice of homogenic and heterogenic strains were separately given one of the three: cyclophosphamide, azathioprine or mizoribine. These drugs were evaluated on the 6th and the 11th day for the immunosuppressive effects expected from a host versus graft reaction. Concerning the homogenic mice that were injected with drugs, on the 11th day, the growth of the tumor was favorably suppressed in comparison with the growth of the control group (A-1) due to the anti-tumor effect of immunosuppressive drugs. We concluded that the 6th day was the most, appropriate day to obtain the results of this assay. Concerning the heterogenic mice, similar results were observed. In the mizoribine-group, we subcutaneously injected 200 mg/kg on alternate days. Yet the implanted tumor grew almost at the same rate as that of the A-1 group. In this group, a histological study showed reduction of the tumor cells and few inflammatory cells. We concluded that this drug was more useful than the others in the SRC assay and the suitable day for judgement was the 6th day.
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PMID:[Comparison of the effects of various immunosuppressive drugs on subrenal capsule assay (SRC assay)]. 223 71

The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future.
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PMID:[Chemotherapy responsiveness of brain tumors in subrenal capsule assay]. 232 45


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