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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proto-oncogenes, which represent the cellular progenitors of the transforming genes harbored by acute transforming oncogenic retroviruses, have been highly conserved during vertebrate evolution. In this report, we have assigned experimentally a subset of proto-oncogenes (SRC, ABL, FES, and FMS-all related to the SRC family) to Chinese hamster chromosomes by Southern filter hybridization analyses of DNAs isolated from both somatic cell hybrids and flow-sorted hamster chromosomes. These results demonstrate that several autosomal linkage groups containing proto-oncogenes originated prior to the radiation and speciation of mammals and have remained remarkably stable for nearly 80 million years.
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PMID:Oncogenes and linkage groups: conservation during mammalian chromosome evolution. 400 99

Receptor-type tyrosine kinases (RTKs) constitute a family of proteins involved in growth and developmental processes. Class III RTKs are characterized by an extracellular region composed of five immunoglobulin-like domains and by a split tyrosine kinase domain. Some of the class III RTKs perform major functions in hematopoiesis and are the focus of this review. They are the colony-stimulating factor-1 (CSF1) and Steel factor (SLF) receptors, encoded by the FMS and KIT protooncogenes, respectively, and the product of the FLT3/FLK2 gene. The structural, biochemical, functional, and pathological features of these three receptors and genes are reviewed.
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PMID:Hematopoietic receptors of class III receptor-type tyrosine kinases. 750 35

We cloned the cDNA for stem cell tyrosine kinase 1 (STK-1), the human homolog of murine Flk-2/Flt-3, from a CD34+ hematopoietic stem cell-enriched library and investigated its expression in subsets of normal human bone marrow. The cDNA encodes a protein of 993 aa with 85% identity and 92% similarity to Flk-2/Flt-3. STK-1 is a member of the type III receptor tyrosine kinase family that includes KIT (steel factor receptor), FMS (colony-stimulating factor 1R), and platelet-derived growth factor receptor. STK-1 expression in human blood and marrow is restricted to CD34+ cells, a population greatly enriched for stem/progenitor cells. Anti-STK-1 antiserum recognizes polypeptides of 160 and 130 kDa in several STK-1-expressing cell lines and in 3T3 cells transfected with a STK-1 expression vector. Antisense oligonucleotides directed against STK-1 sequences inhibited hematopoietic colony formation, most strongly in long-term bone marrow cultures. These data suggest that STK-1 may function as a growth factor receptor on hematopoietic stem and/or progenitor cells.
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PMID:STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. 750 45

Three receptor molecules, belonging to the class III of receptor tyrosine kinases, namely the receptors for colony-stimulating factor 1, CSF1R (product of the FMS proto-oncogene) and Steel factor, SLFR (product of the KIT proto-oncogene), as well as the recently identified FLT3/FLK2 gene product, appear to play distinct roles in normal hematopoietic differentiation. Their potential role in leukemic hematopoiesis has been approached by expression studies in hematopoietic malignancies, especially in acute leukemias of the myeloid and lymphoid lineages. We present here a review of available data, and discuss the possible significance and potential applications of these results.
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PMID:The expression of FMS, KIT and FLT3 in hematopoietic malignancies. 751 7

In order to better understand the role of transcription in cellular processing of damage in specific DNA sequences, we have used an in vitro differentiation system to modulate the activity of the MYC gene. When human HL60 promyelocytic cells differentiate in vitro, the transcriptional activity of the MYC gene is down-regulated. We have shown that in the expressed MYC gene, 56% of UV-induced cyclobutane pyrimidine dimers (CPDs) are removed within 18 h and the transcribed strand is selectively repaired. However, late in differentiation, when the MYC gene is maximally down-regulated, only 15% of the CPDs are removed within the same period. During early differentiation, the MYC gene is regulated by a block to transcription elongation at the 5' end of the first intron. Our results reveal no significant difference in the rate of CPD removal between the restriction fragments upstream and downstream of this elongation block. Furthermore, both strands of each fragment exhibit similar repair characteristics. In contrast, the constitutively expressed FMS gene exhibits proficient removal of CPD in both the differentiated and undifferentiated cells. Furthermore, the repair appears to be more proficient at the 5' end (exon 1) than in the 3' end of the gene about 35 kilobases downstream from exon 1. Since efficient repair of the active FMS gene is maintained in the differentiated cells the loss of repair competence seen in MYC is more likely associated with its reduced transcriptional activity than with a decrease in the overall repair capacity of the terminally differentiated cells.
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PMID:DNA repair in the MYC and FMS proto-oncogenes in ultraviolet light-irradiated human HL60 promyelocytic cells during differentiation. 752 33

The FLT3 gene encodes an hematopoietic receptor related to the receptors for colony-stimulating factor 1, FMS, and for Steel factor, KIT. The extracellular part of these molecules is exclusively composed of five immunoglobulin (Ig)-like domains, designated 1 to 5, from the amino terminus to the carboxyl terminus of the extracellular region. We have isolated a unique murine FLT3 cDNA that codes for a variant isoform of FLT3, devoid of the fifth Ig-like domain, by comparison with the prototypic form. The corresponding mRNA is the result of a splicing event that leads to the elimination of two coding exons. mRNA coding for this variant was detected in almost all the tissues expressing the mRNA coding for the prototypic molecule, although at a lower level. Ligand-induced tyrosine phosphorylation of the two isoforms was equivalent in COS-1 transfected cells, indicating that the fifth Ig-like domain is not strictly necessary for either ligand-binding or kinase activation.
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PMID:Identification and characterization of a functional murine FLT3 isoform produced by exon skipping. 753

Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobulinlike domains in their extracellular regions are classified as subclasses III, IV, and V, respectively. Conservation of the exon/intron structure of the downstream part of the human KIT, FMS, and FLT3 genes that encode RTK of subclass III together with the particular chromosomal localization of these genes suggests that RTKIII genes have evolved from a common ancestor by cis and trans duplications. To strengthen this model of evolution and to determine if it can be extended to RTKIV and V genes, we constructed a phylogenetic tree of RTKIII, IV, and V on the basis of a multiple alignment of their catalytic tyrosine kinase domain sequences and determined the exon/intron structure of PDGFRA (subclass III), FGFR4 (subclass IV), and FLT4 (subclass V) genes in their downstream part. Phylogenetic analyses with amino acid or nucleotide sequences both resulted in one most parsimonious tree. The phylogenetic trees obtained indicate that all three subclasses are well individuated and that RTKIII and RTKV are closer to each other than RTKIV. Furthermore, RTKIII and FLT4 (subclass V) genes possess the same exon/intron structure in their downstream part while the structure of the RTKIV genes is very similar to that of RTKIII and FLT4. Both approaches are in complete agreement and indicate that RTKIII, IV, and V genes most probably evolved from a common ancestor already "in pieces" by successive duplications involving entire genes.
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PMID:Molecular evolution of the genes encoding receptor tyrosine kinase with immunoglobulinlike domains. 756 29

FMS is a complex condition mainly characterized by the presence of chronic pain. The nature of this complaint thus demands assessment in a hierarchal fashion of the various components of the pain system ranging from the nociceptor through to complex central pain-processing mechanisms. The condition is common and represents the most important defined chronic pain syndrome. Elucidation of the mechanisms and better management of FMS will result in improved knowledge of a whole range of related chronic pain syndromes. The database in FMS is necessarily large but does need to be focused according to the need of the person constructing the database and the need of the individual with FMS. As our understanding of FMS evolves, better ways of assessing the various dimensions of the problem will be devised. Perhaps the challenge we face is to bring all the parts together. In doing so, we may find there is a single essential component that links all the clinical features together, which correlates well with severity, disability and outcome, which is amenable to treatment programs, and which is measurable. The search for the soul of the "elephant" of FMS continues.
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PMID:A database for fibromyalgia. 763 Oct 42

The FLT3 gene encodes a receptor tyrosine kinase that is closely related to two well-known receptors, KIT and FMS, that regulate with their respective ligands, stem cell factor (SCF) and macrophage colony-stimulating factor (M-CSF), proliferation and differentiation of hematopoietic cells. The ligand for FLT3, FL, is active in both soluble and membrane-bound forms. We examined expression of FL and FLT3 mRNA in a panel of some 110 continuous human leukemia-lymphoma cell lines from all major hematopoietic cell lineages by Northern blot analysis. FLT3 mRNA is expressed primarily in pre-B cell lines, myeloid and monocytic cell lines whereas FL mRNA was detected in most cell lines from all cell lineages. Analysis of FLT3 receptor protein expression examined with a specific anti-FLT3 monoclonal antibody and flow cytometry in 17 cell lines confirmed the results obtained at the mRNA level. Forty of 110 cell lines displayed both receptor and ligand mRNA suggesting a possible autocrine or intracrine stimulation. In normal hematopoietic cells expression of FLT3 was reported to be associated with CD34 positivity, a cell surface marker of immature and precursor cells. No correlation between FLT3 and CD34 expression was found in the cell lines analyzed. These studies served to illustrate further the importance of the FL-FLT3 ligand-receptor system in the regulation of hematopoietic cells.
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PMID:Expression of FLT3 receptor and FLT3-ligand in human leukemia-lymphoma cell lines. 764 26

Galanin (GAL) has recently emerged as an important neuroendocrine regulator which participates in the control of several pituitary and hypothalamic hormones. Our earlier observation that GAL stimulates LHRH release from nerve terminals of the median eminence as well as basal LH and LHRH-induced LH secretion from pituitary cells in vitro prompted us to evaluate whether endogenous GAL plays a role in regulation of the physiologically occurring preovulatory surges of gonadotropins and PRL. Proestrous female rats were passively immunized against GAL using a high affinity sheep antirat GAL serum (FMS-FJL 17-5). Animals were implanted during diestrus with indwelling atrial cannulae. On the expected day of proestrus, rats received 1 ml of either normal sheep serum or GAL antiserum (GAL-AS), iv, 1 h before blood sampling started. Blood samples (0.5 ml) were collected at hourly intervals from 1400-2300 h, and plasma levels of LH, FSH, and PRL measured by RIA. At several time intervals after GAL-AS administration, the maximum binding ability of the rat plasma was evaluated using standard saturation assays. High neutralizing levels of immunoglobulins were present throughout the experimental period. GAL passive immunization blunted the LH preovulatory surge by 30%. Although maximum LH levels were unaffected by the treatment, the area under the secretory curve and LH levels at 1700, 1900, and 2000 h were significantly reduced. Conversely, FSH secretion was not significantly altered for either maximum FSH levels or area under the curve. However, FSH levels were significantly diminished in GAL-AS-treated rats at 1700 h. GAL passive immunization selectively reduced the plateau phase of the preovulatory surge of PRL. No significant differences were observed in the initiation of the surge or maximum PRL levels, whereas PRL levels were significantly reduced from 1700 to 2200 h. In addition, the area under the PRL curve was diminished in GAL-AS-treated animals by 40%. In conclusion, our results clearly demonstrate that endogenous GAL is involved in control of the preovulatory surges of LH and PRL without altering the FSH surge. In addition, they provide, for the first time, evidence of an important role for endogenous GAL in the regulation of physiological events leading to ovulation.
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PMID:Endogenous galanin modulates the gonadotropin and prolactin proestrous surges in the rat. 767


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