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)

We report the identification of ligands for Tyro 3 (alternatively called Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein S, a protease regulator that is a potent anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings that the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracellular signaling via a G protein-coupled cell surface receptor. Proteases and protease regulators that also activate specific cell surface receptors may serve to integrate coagulation with associated cellular responses required for tissue repair and growth, as well as to coordinate protease cascades and associated cellular responses in other systems, such as those involved in growth and remodeling of the nervous system.
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PMID:The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. 786 73

To gain insight into the signal transduction pathways utilized by the Wnt-1-responsive mammary epithelial cell line C57MG, we screened for non-src family member tyrosine kinases expressed in these cells using a polymerase chain reaction-based technique. We identified five cDNA clones encoding receptor tyrosine kinases for which the ligand is known (fibroblast growth factor receptor, platelet-derived growth factor receptor, epithelial growth factor receptor, insulin receptor, and insulin-like growth factor receptor), two putative receptor tyrosine kinases for which the ligand remains to be identified (the products of ryk and the mouse klg homolog), and a novel tyrosine kinase. We cloned cDNAs encoding both the murine and human homologs of this kinase, the sequences of which were subsequently published under the names sky (Ohashi, K., Mizuno, K., Kuma, K., Miyata, T., and Nakamura, T. (1994) Oncogene 9, 699-705) and rse (Mark, M. R., Scadden, D. T., Wang, Z., Gu, Q., Goddard, A., and Godowski, P. J. (1994) J. Biol. Chem. 269, 10720-10728). Mouse sky RNA levels are abundant in mammary tumors derived from transgenic mice that express wnt-1, fgf-3, or both oncogenes in their mammary glands. However, little or no expression of sky is detected in mammary glands from virgin animals or in preneoplastic mammary glands from wnt-1 transgenic mice. Moreover, we find that the human homolog of sky is expressed at elevated levels when normal human mammary epithelial cells are rendered tumorigenic by the introduction of two viral oncogenes. Transient transfection of the human SKY cDNA into the quail fibrosarcoma cell line QT6 reveals that SKY is an active tyrosine kinase that augments the level of cellular phosphotyrosine. Introduction of murine Sky into RatB1a fibroblasts by retrovirus-mediated gene transfer results in morphological transformation, growth in soft agar, and the formation of tumors in nude mice. These data raise the possibility that the Sky tyrosine kinase is involved in the development and/or progression of mammary tumors.
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PMID:Mouse mammary tumors express elevated levels of RNA encoding the murine homology of SKY, a putative receptor tyrosine kinase. 789 35

The bean grp1.8 full-length promoter is specifically active in vascular tissue during normal development of tobacco. Deletion of a negative regulatory element resulted in ectopic activity of the promoter in cortical cells of hypocotyls, roots and stems. A 169 bp fragment (-205 to -36) of the grp1.8 promoter conferred vascular-specific expression to CaMV 35S minimal promoters whereas a 141 bp fragment (-205 to -64) strongly activated these minimal promoters both in vascular and cortical cells. These experiments defined a new regulatory element (VSE) that is essential for vascular-specific expression and is located between -64 and -36. The 141 bp grp1.8 promoter sequence had enhancer-like properties as it was active in both orientations. A 24 bp sequence (bp -119 to -96, corresponding to the SE1 regulatory element) enhanced expression from several minimal promoters strongly but unspecifically, whereas a 26 bp sequence (-98 to -73, corresponding to the RSE regulatory element) induced vascular-specific expression. Thus, the grp1.8 promoter is regulated by a combinatorial mechanism that can integrate the action of different, non-additively acting regulatory elements into vascular-specific expression.
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PMID:Vascular expression of the grp1.8 promoter is controlled by three specific regulatory elements and one unspecific activating sequence. 794 28

Zygotes of S. purpuratus were injected with synthetic mRNAs encoding rodent brain neurotransmitter receptors, and specific developmental phenotypes were produced on addition to the sea water of the respective ligands. Most of these experiments were carried out with a mouse serotonin receptor (5HT-R) mRNA, though exactly comparable results were obtained with a rat muscarinic acetylcholine receptor (MAChR) mRNA; these receptors are expected to couple to the same endogenous signal transduction system. We show by whole mount in situ hybridization that the injected mRNAs diffuse to all of the early blastomeres, and that they are translated in vivo. Three specific phenotypes were reproducibly observed. The most severe, occurring at highest levels of injected mRNA, was a cleavage arrest phenotype in which no overtly differentiated cells ever appear, though the embryos remain alive for at least 72 h. A gastrular arrest (GA) phenotype is generated in appreciable fractions of embryos developing from eggs injected with lower levels of mRNA. In GA embryos the blastocoel is filled with disorganized mesenchyme cells, including pigment cells and skeletogenic cells; there is no archenteron; and the entire ectoderm expresses an oral ectoderm cell surface marker. The least severe phenotype that we recognized displays an altered arrangement of spiculogenic foci (RSE phenotype), generating a ring of extra spicules that are properly positioned with respect to the animal/vegetal axis, but that lack any reference to the oral/aboral axis. However, use of cytological and molecular markers demonstrates that RSE embryos retain normal spatial patterns of aboral and oral ectoderm. They develop a fully formed archenteron, but fail to form either a stomodaeum or a ciliated band. RSE embryos can be produced in embryos expressing the 5HT-R by exposure to serotonin, beginning as late as 12 h postfertilization (pf). All of the morphogenetic processes affected in RSE embryos depend in normal embryos on intercellular interactions occurring at the blastula-gastrula stages of development.
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PMID:Ligand-dependent stimulation of introduced mammalian brain receptors alters spicule symmetry and other morphogenetic events in sea urchin embryos. 818 47

Ss who reported UFO experiences were divided into those whose experiences were nonintense (e.g., seeing lights and shapes in the sky) and those whose experiences were intense (e.g., seeing and communicating with aliens or missing time). On a battery of objective tests Ss in these 2 groups did not score as more psychopathological, less intelligent, or more fantasy prone and hypnotizable than a community comparison group or a student comparison group. However, Ss in the UFO groups believed more strongly in space alien visitation than did comparison Ss. The UFO experiences of Ss in the intense group were more frequently sleep-related than the experiences of Ss in the nonintense group. Among the combined UFO Ss, intensity of UFO experiences correlated significantly with inventories that assessed proneness toward fantasy and unusual sensory experiences. Implications are discussed.
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PMID:Close encounters: an examination of UFO experiences. 828 33

To define the histogenesis and cell origin of Kaposi sarcoma (KS), we cultured KS cells without retrovirally conditioned media from three HIV seropositive AIDS patients and then attempted to raise mouse hybrid monoclonal antibodies (Mabs) specific to these AIDS-KS cells. After both in vivo and in vitro immunization trials, all putative Mabs reacted positively to KS cells but also non-specifically with other human (CH5 and OM) and non-human (RSE-1) control endothelial cell lines. To overcome this crossreactivity, we further "absorbed" previously cloned hybrids and pre-hybrid splenocytes by incubating them with the control endothelial cell lines to eliminate splenocytes and/or hybridomas reactive to normal endothelium. Whereas absorption successfully eliminated immunoreactivity to control endothelium, it also excluded reactivity to KS cells. These findings (lack of specific antigenicity and immunoresponsiveness of KS similar to non-KS control endothelium) suggest that AIDS-KS cells are neither antigenically transformed nor neoplastic, but instead represent dedifferentiated or transdifferentiated endothelium which retains immunogenicity of its original endothelial cell prototype.
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PMID:Absence of monoclonal antibody detectable Kaposi sarcoma-specific antigens on lesion-derived cultured cells. 842 58

Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hematopoietic system and compared the pattern of expression with that of Ufo. Both receptors were abundantly expressed in differentiating embryonic stem cells, yolk sac blood islands, para-aortic splanchnopleural mesoderm, fractionated AA4+ fetal liver cells, and fetal thymus from day 14 until birth. Although Ufo was expressed at moderate levels in adult bone marrow, expression of Dtk in this tissue was barely detectable. In adult bone marrow subpopulations fractionated using counterflow centrifugal elutriation, immunomagnetic bead selection for lineage-depletion and FACS sorting for c-kit expression, very low levels of Dtk and/or Ufo were detected in some cell fractions. These results suggest that Dtk and Ufo are likely to be involved in the regulation of hematopoiesis, particularly during the embryonic stages of blood cell development.
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PMID:The Dtk receptor tyrosine kinase, which binds protein S, is expressed during hematopoiesis. 864 60

The receptor tyrosine kinase Dtk/Tyro 3/Sky/rse/brt/tif is a member of a new subfamily of receptors that also includes Axl/Ufo/Ark and Eyk/Mer. These receptors are characterized by the presence of two immunoglobulin-like loops and two fibronectin type III repeats in their extracellular domains. The structure of the murine Dtk gene has been determined. The gene consists of 21 exons that are distributed over 21 kb of genomic DNA. An isoform of Dtk is generated by differential splicing of exons from the 5' region of the gene. The overall genomic structure of Dtk is virtually identical to that determined for the human UFO gene. This particular genomic organization is likely to have been duplicated and closely maintained throughout evolution.
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PMID:Analysis of the murine Dtk gene identifies conservation of genomic structure within a new receptor tyrosine kinase subfamily. 880 74

brt encodes a receptor-type protein-tyrosine kinase and was isolated from fetal mouse brain by using a PCR-mediated cloning procedure; this gene is expressed preferentially in the brain of both embryo and adult. Chromosomal locations of the mouse and rat brt genes were determined by fluorescence in situ hybridization using a mouse cDNA fragment as a probe. The brt gene was localized to mouse Chromosome 2F1 and rat Chromosome 3q36.1, where a conserved linkage homology has been identified between the two species. Interspecific backcross analysis genetically demonstrated no recombination between the mouse BRT locus and D2Mit63.
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PMID:Chromosomal mapping of the mouse and rat brt genes. 907 Sep 38

Using a PCR-based cloning technique, we isolated a series of protein tyrosine kinases (PTKs) expressed in a cell line of esophageal squamous cell carcinoma. Sequence analysis revealed 10 different kinds of PTKs of the receptor type [epidermal cell growth factor receptor, insulin-like growth factor I receptor, fibroblast growth factor receptor 4, eck, erk, discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak), HEK2, HEK8, axl and sky] and one PTK of the nonreceptor type (tyk2). Subsequently, we examined the expression of the transcripts of these 11 genes in paired samples of normal and carcinomatous esophageal tissues obtained from 12 cases of esophageal cancer. We found that all 11 gene transcripts were expressed in both carcinomatous and normal tissues, and 6 of them were significantly overexpressed in carcinomatous tissues relative to adjacent normal tissues. Among these, the magnitude of mRNA expression of DDR/trkE/Cak PTK was positively correlated with the proliferative activity of carcinoma cells, but not with their degree of differentiation. Immunohistochemically, DDR was expressed in both normal and cancerous esophageal cells. The intensity of the expression was higher in cancer than normal tissue. In addition, we confirmed the expression of two isoforms of DDR/trkE/Cak in normal and cancerous esophagus. Our study suggests that DDR/trkE/Cak plays an important role in the regulation of proliferation of esophageal cancer.
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PMID:Overexpression of protein tyrosine kinases in human esophageal cancer. 939 43


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