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)

Hepatocyte growth factor/scatter factor (HGF-SF), a multifunctional cytokine, is the ligand for the met receptor tyrosine kinase. Multiple met mRNAs of 8, 7, 5, 3 and 1.6-kb in size have been identified in human cell lines and tissue. To investigate the biological function of these various isoforms we have isolated cDNA clones corresponding to some of the differentially spliced met mRNAs. Characterization of these cDNAs suggests that by alternative splicing and possibly by use of distinct transcription initiation sites the met HGF-SF receptor is expressed in various isoforms. We have demonstrated that there are two met 8-kb mRNAs that differ through alternative splicing of a 54-bp exon that maintains the open reading frame such that these proteins differ by only 18 aa in their extracellular domain. The -54-bp form corresponds to the most abundant 8-kb met RNA and encodes the p190 met alpha beta heterodimer. In contrast the +54-bp mRNA encodes a protein of 170 kd that is not cleaved yet is expressed at the cell surface and has in vitro kinase activity. The 7-kb mRNA differs by alternative splicing such that it encodes a protein with a distinct amino terminus. Unlike these met RNAs, the 1.6-kb mRNA has new 5' and 3' sequences and encodes a protein that shares homology with the extracellular domain of the met RTK but has a unique carboxy terminus. Thus multiple met RNAs encode proteins that differ in both the extracellular ligand binding domain and within the cytoplasmic domain suggesting that these different met isoforms may have distinct biological activities.
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PMID:Isoforms of the met receptor tyrosine kinase. 838 Jul 36

Using a polymerase chain reaction-based approach we have isolated and characterized a cDNA (HPK-6) from human placental RNA encoding a novel receptor protein tyrosine kinase. This receptor tyrosine kinase has a unique extracellular domain, with an immunoglobulin-like domain at the amino terminus followed by three EGF-like cysteine repeats and three fibronectin type III repeats, giving the HPK-6 gene extracellular domain a novel combination of structural motifs. A comparison of the HPK-6 sequence with other receptor tyrosine kinases shows that the HPK-6 gene is the human homolog of the murine tek gene and very closely related to the recently described receptor tyrosine kinase tie. The HPK-6 gene is expressed predominantly in placenta and lung, with a lower level in umbilical vein endothelial cells, brain and kidney. The HPK-6 cDNA, when transfected into COS-7 cells, encodes a 140-kDa protein with in vitro kinase activity.
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PMID:Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta. 838 58

A wide range of growth and differentiation processes are regulated by the signalling of receptor tyrosine kinases (RTKs). We have developed a nested polymerase chain reaction (PCR) procedure with degenerate primers, and used it to identify RTKs expressed in murine fetal thymus. A novel RTK, called FLT4, and the murine homologue of FLT were found, and their PCR fragment sequences were used to isolate larger cDNA clones spanning the complete coding regions of these receptors. FLT4 was found to contain an extracellular region similar to the corresponding sequences of FLT and Flk-1, containing seven immunoglobulin domains.
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PMID:Molecular cloning of murine FLT and FLT4. 839 64

To identify receptor tyrosine kinases (RTKs) critical to early hematopoiesis, we performed polymerase chain reaction-based cloning from yolk sac and highly enriched bone marrow hematopoietic stem cells (HSCs). Characterization of two novel genes of their full-length cDNA sequences revealed that they were mouse homologues of the endothelial cell RTK genes, TIE and TEK. They shared a unique structural property of coexistent immunoglobulin-like domain, epidermal growth factor-like repeats, and fibronectin type III repeats in their extracellular domains. Both genes were expressed in a similar fashion in adult tissues and primitive hematopoietic cells, predominantly in the bone marrow HSCs.
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PMID:Molecular cloning and characterization of mouse TIE and TEK receptor tyrosine kinase genes and their expression in hematopoietic stem cells. 839 28

Motor neurons stimulate their postsynaptic muscle targets to synthesize neurotransmitter receptors. Polypeptide signaling molecules may mediate this inductive interaction. Here we report the purification of ARIA, a protein that stimulates the synthesis of muscle acetylcholine receptors, and the isolation of ARIA cDNA. Recombinant ARIA increases acetylcholine receptor synthesis greater than 3-fold, and it induces tyrosine phosphorylation of a 185 kd muscle protein. The ARIA cDNA hybridizes with mRNAs that are expressed in the spinal cord from E4, a time prior to the onset of neuromuscular synapse formation, through adulthood. By E7, hybridizing mRNAs are concentrated in motor neurons. Chicken ARIA is homologous to the rat Neu differentiation factor and human here-gulin, ligands for the receptor tyrosine kinase encoded by the neu (c-erbB2, HER2) proto-oncogene. Our data suggest that members of the ARIA protein family promote the formation and maintenance of chemical synapses and, furthermore, that receptor tyrosine kinases play important roles in this process.
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PMID:ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family. 845 70

Using the polymerase chain reaction with degenerate oligonucleotides derived from conserved motifs within the catalytic kinase domain of protein tyrosine kinases, and RNA extracted from embryonic stem cells, sequences that encode a segment of the kinase domain of several potentially novel receptor tyrosine kinases (RTKs) have been identified. One of these was selected for further study because in Northern analysis it hybridized to RNA from multipotential hematopoietic cell lines, but not from lines representative of lineage-committed cells. A cDNA for this receptor, designated developmental tyrosine kinase (DTK), was isolated and encodes a protein with structural similarities to AXL. Together these receptors form a new class of RTK. DTK is expressed in a number of human leukemic cell lines, and in the blasts of 6 of 11 patients with acute myeloid leukemia (AML) analyzed. The structure of DTK suggests that it may function as a cell adhesion molecule, and mediate cell-to-cell or cell-matrix interactions between hematopoietic cells and their respective microenvironments.
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PMID:Identification of a novel receptor tyrosine kinase expressed in acute myeloid leukemic blasts. 852 51

A new gene belonging to the Eph/Eck/Elk receptor tyrosine kinase family has been cloned from mouse brain. The gene maps to mouse chromosome 4. In the adult brain it is expressed exclusively and abundantly in the hippocampus. We propose to name it Ebk (embryo brain kinase), as in situ hybridisation shows expression in many parts of the developing mouse brain. The most abundant expression is in the subcommissural organ, and the earliest expression is in the forebrain neural folds, in rhombomeres 2-6, and in somites and heart. Other regions positive at various stages include the cochlear duct, trigeminal ganglion, lung, first branchial arch, and tooth primordia. Also positive are areas of mesenchyme underlying various epithelia during morphogenesis, especially in the mouth and nose, as well as in the eyelids and toes. We compare these patterns with the available data on the 12 other known members of this gene family. Most of them, like Ebk, are expressed in brain (especially adult hippocampus and embryonic rhombomeres) and in organs rich in epithelia (especially lung), although the spatial and temporal patterns differ. We suggest that combinatorial patterns of these receptors act as labels for the regional identity of neurons and epithelia, and could mediate fine control of neurite pathfinding and epithelial morphogenesis.
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PMID:Embryo brain kinase: a novel gene of the eph/elk receptor tyrosine kinase family. 854 Dec 19

A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains immunoglobulin-like loops and epidermal growth factor [EGF] homology domains), is expressed in vascular endothelial and hematopoietic cells. We generated monoclonal antibodies (MoAbs) against the extracellular domain of TIE and a polyclonal antibody against the TIE carboxyterminus and used them to analyze expression of TIE in hematopoietic cells. Western blotting detected two forms of TIE protein with a molecular mass of 135 and 130 kD in hematopoietic and endothelial cells. Northern blotting analysis revealed that TIE was expressed preferentially in undifferentiated cell lines, especially when megakaryocytic, but not erythroid differentiation was induced. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that TIE was predominantly expressed in the human hematopoietic progenitor fraction, CD34+ cells. Fluorescence-activated cell sorting (FACS) showed that 42% of CD34+ and 17% of KIT-positive (KIT+) cells were TIE-positive (TIE+). The majority (81%) of the primitive hematopoietic stem cells, CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term culture-initiating cells (LTC-IC) showed that the TIE+ fraction contained more primitive cells than the TIE- fraction. Some TIE+ cells were in the CD34- fraction, which were CD19+ and CD20+ (B cells). These findings indicate that TIE has a unique spectrum of expression in primitive hematopoietic stem cells and B cells. Although its ligand has not been identified, TIE and its ligand may establish a novel regulatory pathway not only in early hematopoiesis, but also in the differentiation and/or proliferation of B cells.
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PMID:Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem cells and B cells. 854 81

The RET proto-oncogene encodes a receptor tyrosine kinase (TK). It has been shown that distinct germline mutations in the RET proto-oncogene are associated with the dominantly inherited cancer syndromes multiple endocrine neoplasia type 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as Hirschsprung disease (HSCR), a congenital disorder characterised by absent enteric innervation. In this study, we have transfected NIH3T3 and PC12 phaeochromocytoma cells with MEN2A (Cys634-> Arg) and MEN2B (Met918-> Thr) RET constructs. Both caused transformation of the NIH3T3 cells and differentiation of PC12 cells. The Ret (MEN2A) and Ret (MEN2B) proteins were constitutively phosphorylated on tyrosine, and their in vitro kinase activity was significantly higher than that of the wild type protein. The MTC cell line TT carries a CYs634-> Trp MEN2A mutation, and we have shown by immunoelectronmicroscopy that Ret is clustered on the cell surface in a manner reminiscent of ligand-induced aggregation of cell surface receptors. RET is activated, as RET/PTC oncogene, by somatic rearrangements which link the TK domain to a constitutive dimerization interface in papillary thyroid carcinomas. We have compared the biological and biochemical activity of the TK domains of the wild type and MEN 2B Ret in the context of the RET/PTC. The results show that the MEN 2B mutation significantly increases the TK domain enzymatic activity suggesting that dimerization may be still necessary for MEN 2B Ret to express its full activity.
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PMID:RET activation by germline MEN2A and MEN2B mutations. 857 Jan 94

The genomic organization of Cek5, a receptor tyrosine kinase of the Eph subfamily, was elucidated utilizing a strategy involving PCR amplification of Cek5 genomic DNA. Cek5 is the first Eph-related kinase for which the exon-intron structure of the entire coding region has been determined. The Cek5 gene spans over 35 kb and comprises at least 16 exons. The exon-intron structure of Cek5 can be correlated with the proposed domain structure of the Eph subfamily, with the exception of an Ig motif in the extracellular domain. Intron positions in the Cek5 gene coincide with the locations of the deletions, substitutions, or insertions that have been described in a number of Eph-related kinases. This suggests that alternative processing plays a major role in generating the structural variability observed in the Eph subfamily. Consistent with this hypothesis, analysis of the Cek5 gene indicate that: (i) a variant form of Cek5 containing an insertion in the juxtamembrane region (Cek5 +) arises through the use of alternative 5' splice sites, and (ii) a soluble form of Cek5 comprising only the extracellular domain (Cek5s) may exists, which originates by alternative polyadenylation. RT-PCR analysis and RNase protection assays revealed the expression of both Cek5 + and Cek5s at various stages of chicken development.
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PMID:Genomic organization and alternatively processed forms of Cek5, a receptor protein-tyrosine kinase of the Eph subfamily. 857 Jan 95


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