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)

Trisomy of chromosome 11 (Ts11) is the second most frequent nonrandom chromosomal change in murine plasmacytomas (PCTs). The frequency of Ts11 is significantly higher in PCTs induced in pristane-conditioned mice infected by Abelson-murine leukemia virus (52%) compared to those induced by pristane alone (8.1%). Although the significance of Ts11 in mouse plasmacytomagenesis is not clearly understood it is hypothesized that a gene or genes located on chromosome (Chr) 11 may specifically promote the development of PCTs in which both oncogenes, c-myc and v-abl, are abundantly expressed. To test this assumption we induced PCTs by three highly effective plasmacytomagenic retroviruses: ABL-MYC, J3V1, and RIM. Nearly 90% of PCTs that arose in BALB/c, (BALB/c x DBA/2N)F1, BALB/c-nu/nu, and 5-month-old SCID mice infected with ABL-MYC virus were trisomic for Chr 11. In contrast, < 10% of PCTs induced by J3V1 or RIM retroviral constructs encompassing either v-myc and v-raf or c-myc and v-Ha-ras oncogenes, respectively, contained Ts11. We have also investigated whether the entire Chr 11 or any particular subregion is preferentially duplicated in the process of ABL-MYC plasmacytomagenesis. By inducing PCTs in F1 heterozygous mice that are carriers of reciprocal translocations involving Chr 11 we found that the duplicated chromosomal region is located distal to the T4Dn breakpoint (11B5 band) on the telomeric segment of Chr 11. The regular duplication of this chromosomal segment strongly suggests the presence of a gene or genes whose amplification is of critical importance for v-abl associated murine plasmacytomagenesis.
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PMID:Nonrandom chromosomal change (trisomy 11) in murine plasmacytomas induced by an ABL-MYC retrovirus. 786 5

We have investigated the role of JAK3 in interleukin 2 (IL-2)-induced signal transduction with a human T cell line, ED40515(-), lacking expression of the IL-2 receptor gamma chain and its sublines transfected with wild-type or mutant cDNAs of the IL-2 receptor gamma chain. Our results demonstrated that the membrane-proximal cytoplasmic region, encompassing the src homology region 2 (SH2)-like subdomain, of the gamma chain is essential for association and activation of JAK3. Furthermore, IL-2-induced activation of JAK3 paralleled induction of the c-myc gene and DNA synthesis but not induction of the c-fos and c-jun genes. These results support the hypothesis that JAK3 plays a pivotal role in the IL-2 receptor-mediated signals for cell growth.
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PMID:Interleukin 2-induced activation of JAK3: possible involvement in signal transduction for c-myc induction and cell proliferation. 808 65

The neuro-intestinal peptide hormone cholecystokinin (CCK)/gastrin has been suggested to have a trophic effect on gastro-intestinal tract in vivo as well as in vitro. In the present study, the human CCK-B/gastrin receptor was expressed in mouse NIH3T3 fibroblasts to investigate the molecular basis of signal transduction pathway of the guanine nucleotide regulatory protein (G protein)-coupled receptor. Human CCK-B/gastrin receptor expressed in NIH3T3 cells coupled efficiently to phosphoinositide hydrolysis and mobilization of intracellular Ca2+, and transduced mitogenic signals assessed by [3H]thymidine incorporation in a dose-dependent manner. Moreover, CCK-8 or gastrin I alone promoted the cell growth in serum-free medium. CCK-8 induced tyrosine phosphorylation of several protein species. Among them, mitogen-activated protein (MAP) kinase was tyrosine phosphorylated and activated in response to CCK-8, as was induced by platelet-derived growth factor (PDGF). In contrast, tyrosine phosphorylation of p125FAK (focal adhesion kinase) was induced by CCK-8 but not by PDGF. CCK-8 as well as gastrin I induced the expression of early responsive genes such as c-fos and c-myc. These results suggest that CCK-B/gastrin receptors might transmit mitogenic signals by cross-talking with the tyrosine kinase cascades.
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PMID:Cholecystokinin-B/gastrin receptor signaling pathway involves tyrosine phosphorylations of p125FAK and p42MAP. 810 29

The BCR-ABL gene plays a central role in the pathogenesis of chronic myelogenous leukemia. Despite a detailed understanding of the regions of BCR and ABL required for transformation by BCR-ABL, little is known about the signalling pathway by which BCR-ABL causes transformation. The nuclear oncogene c-myc plays a critical role in BCR-ABL transformation. Levels of c-myc RNA are high in cells transformed by BCR-ABL, and overexpression of dominant negative forms of myc blocks transformation by BCR-ABL. These findings suggest that myc may be a useful therapeutic target in BCR-ABL-related leukemias.
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PMID:The role of myc in transformation by BCR-ABL. 825 15

ABL-MYC, a retrovirus that coexpresses v-abl and c-myc, was used to infect six BALB/c mice that had been immunized twice with a KLH-conjugated peptide that consisted of the 18 carboxyterminal amino acids of protein kinase C-eta (PKC-eta). All mice developed transplantable, monoclonal plasmacytomas, and five out of six plasmacytomas secreted antigen-specific antibodies, even after transplantation. All these antibodies recognized PKC-eta on Western blots of crude cell lysates and did not cross react with other isoforms of the PKC family.
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PMID:Induction of plasmacytomas that secrete monoclonal anti-peptide antibodies by retroviral transformation. 828 88

Primary diffuse infiltrative cancer of the large bowel shows poor prognosis. A human rectal cancer cell line, designated as SRM, was established from the metastatic lymph node of a 35-year-old female patient. SRM cells have been cultured with RPMI-1640 medium supplemented with 10% fetal calf serum and grew as monolayers, showing a tendency to pile up. The doubling time of this cell line was 23.0 hours, and the modal number of chromosomes was 64 at passage 14. The cells produced CA19-9 and TPA in the spent medium and formed tumors in nude mice, the histology of which was similar to that of the primary tumor. CA19-9 in the cytoplasma of the transplanted tumor cells was demonstrated by the ABC method and the c-myc oncogene was amplified in the transplanted tumor in nude mice.
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PMID:[Establishment and characterization of a human rectal cancer cell line, SRM from primary diffuse infiltrating type cancer]. 834 49

Interleukin 6 (IL-6) induces in M1 myeloblastic cells growth arrest and terminal differentiation toward monocytes. It is reported here that IL-6 reduced by 5- to 20-fold the tyrosine phosphorylation of cellular proteins in these cells. The same-fold reduction was also observed in M1 cells that were transfected with the BCR-ABL deregulated protein kinase. In these stable clones, the levels of tyrosine phosphorylation of cellular proteins were 30- to 100-fold higher than in the parental cells. IL-6 did not reduce the expression levels or the inherent tyrosine kinase activity of BCR-ABL p210. By measuring the protein-tyrosine-phosphatase (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) activity in crude cell lysates, we found that protein dephosphorylation resulted, at least partially, from induction of PTPase activity by IL-6. The induction of PTPase in the BCR-ABL-transfected clones was not sufficient to confer the minimal protein phosphorylation levels characteristic of IL-6-treated cells. Yet, the transfected M1 clones showed normal growth and differentiation responses to IL-6. None of the gene responses to IL-6 including suppression in the levels of c-myc, c-myb, and cyclin A mRNA; junB and c-jun mRNA induction; and dephosphorylation of retinoblastoma protein were rescued by the BCR-ABL oncogene. The functional relevance of PTPase induction by IL-6 is discussed.
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PMID:Induction of protein-tyrosine-phosphatase activity by interleukin 6 in M1 myeloblastic cells and analysis of possible counteractions by the BCR-ABL oncogene. 842 78

Abelson murine leukemia virus (A-MuLV), a retrovirus that expresses the v-abl oncogene, characteristically induces pre-B-cell lymphomas following in vivo infection of BALB/c mice or in vitro infection of suspensions of fetal liver or bone marrow cells. ABL-MYC, a retrovirus that expresses both v-abl and c-myc, induces solely plasmacytomas in BALB/c mice. To investigate how the addition of overexpression of c-myc to that of v-abl accomplishes this dramatic change in the phenotype of the cells transformed by these closely related retroviruses, we utilized helper-free A-MuLV (psi 2) and ABL-MYC (psi 2) in vitro to infect suspensions of cells from different lymphoid tissues and purified immature and purified mature B cells. As expected, A-MuLV(psi 2) induced only pre-B-cell lymphomas in vivo and in vitro when immature B cells were present. ABL-MYC(psi 2), on the other hand, produced only plasmacytomas, even when purified immature B lymphocytes were infected in vitro. Although the A-MuLV(psi 2)-induced pre-B-cell lymphomas express easily detectable levels of c-myc mRNA, maturation into more-mature forms of B lymphocytes is blocked. The constitutively overexpressed c-myc in the ABL-MYC retrovirus abrogates this block, permits maturation of infected immature B cells, and yields transformed plasma cells.
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PMID:Addition of constitutive c-myc expression to Abelson murine leukemia virus changes the phenotype of the cells transformed by the virus from pre-B-cell lymphomas to plasmacytomas. 845 30

Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified. Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines. The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter. Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5. About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM. Thus OSM is one of the common targets of a subset of cytokines that activate STAT5. The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM. Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine.
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PMID:Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. 860 75

Interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to activate JAK2 in various cells, but the role of JAK2 in IL-3 or GM-CSF receptor signal transduction is largely unknown. We have now examined the role of JAK2 in GM-CSF-induced signaling events in BA/F3 cells. In BA/F3 cells expressing hGMR, activation of JAK2 by hGM-CSF requires the box1 region of hGMR beta. Dominant negative JAK2 (delta JAK2), which lacked the kinase domain suppressed mIL-3 or hGM-CSF-induced c-fos promoter activation as well as c-myc promoter activation/cell proliferation, thereby suggesting that JAK2 is involved in the signaling of both pathways. Further analyses of the role of JAK2 in c-fos gene activation in BA/F3 cells expressing hGMR revealed that delta JAK2 inhibited hGM-CSF-induced phosphorylation of Shc and protein tyrosine phosphatase 1D. Within hGMR beta, the several tyrosine residues which exist are related to activation of Shc or protein tyrosine phosphate 1D, and are phosphorylated in response to hGM-CSF stimulation. In addition, we observed that delta JAK2 inhibited hGM-CSF-induced phosphorylation of hGMR beta. Taken together, our results suggest that JAK2 activated by the box1 region of hGMR mediates hGM-CSF-induced c-fos promoter activation through phosphorylation of hGMR.
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PMID:JAK2 is essential for activation of c-fos and c-myc promoters and cell proliferation through the human granulocyte-macrophage colony-stimulating factor receptor in BA/F3 cells. 864 82


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