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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The translocation t(15;17)(q22;q21) is seen exclusively in patients with acute promyelocytic leukemia (APL) and in the promyelocytic blast crisis of chronic myeloid leukemia (CML). This translocation juxta-poses the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor-alpha (RARA) gene on chromosome 17, resulting in the formation of a chimeric mRNA transcript. We describe a patient with the microgranular variant form of APL, with no detectable cytogenetic abnormality of either chromosomes 15 or 17, who nevertheless had juxtaposition of PML and RARA genes and expressed a chimeric transcript. Conventional cytogenetics showed the karyotype 46,XY,d-er(3)t(3;8)(p25;q12). Fluorescent in situ hybridization (FISH) with paints for chromosomes 8, 15, and 17 confirmed the presence of structurally intact chromosomes 15 and 17 and trisomy for chromosome 8q. Nevertheless, FISH using cosmid probes for PML and RARA showed their juxtaposition on one chromosome 15 homolog. Both genes were also present on their normal homologs; in addition, part of the RARA gene was still present on the remaining chromosome 17. DNA analysis by Southern blotting, performed with a variety of probes including PML, RARA and retinoic acid receptor-beta (RARB), showed a rearrangement in PML. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the existence of hybrid transcripts of 276, 455 bp and 623 bp, from PML-RARA on the der(15) chromosome, consistent with alternate exon splicing of the long form of the transcript occurring in 50% to 60% of patients with APL. Our results show that APL patients with cytogenetically normal chromosomes 15 and 17 may, nevertheless, have involvement of both PML and RARA genes defining a subgroup of APL, t(15;17)-negative/PML-RARA-positive which is analogous to Philadelphia chromosome-negative/BCR-ABL-positive CML. In this case, the presence of chimeric transcripts suggests that treatment with all-trans RA may be warranted in APL, even in the absence of detectable cytogenetic change, showing the usefulness of RT-PCR or FISH to aid diagnosis.
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PMID:Interstitial insertion of retinoic acid receptor-alpha gene in acute promyelocytic leukemia with normal chromosomes 15 and 17. 818 Mar 90

The genes for the long form of the human and the short form of the mouse PRL receptors were transfected independently into NIH 3T3 cells. Reverse transcriptase-polymerase chain reaction indicated that the transfectant designated LFH contained message for only the long form and the transfectant designated SFM had message for only the short form of the receptor. Both transfectant cell lines specifically bound lactogenic hormones with high affinity and responded to PRL in culture with a 2- to 3-fold increase in cell number preceded by transient activation of mitogen-activated protein kinase. After a PRL-responsive casein-chloramphenicol acetyl transferase (CAT) construct was introduced into both LFH and SFM cells, CAT activity was induced by PRL only in the LFH-CAT cells. Thus, while the long form of the receptor can transduce the differentiation signal, both the long and the short forms of the receptor can signal the cells to grow.
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PMID:Transduction of prolactin's (PRL) growth signal through both long and short forms of the PRL receptor. 861 11

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel neuropeptide that produces its biological effects by interacting with G protein-coupled receptors. Molecular cloning of the PACAP receptor revealed the existence of five splice variant receptor forms differing in the third intracellular loop region, with four variants activating both adenylyl cyclase and phosphoinositide phospholipase C and one variant activating only adenylyl cyclase (Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P. H., and Journot, L. (1993) Nature 365, 170-175). Here, we report cloning of a novel PACAP receptor variant, designated PACAPR TM4 (transmembrane domain IV), that differs from the previously cloned short form of the PACAP receptor (PACAPR) primarily by discrete sequences located in transmembrane domains II and IV. Reverse transcriptase-polymerase chain reaction and primer extension analyses demonstrated tissue-specific differential expression of mRNAs encoding PACAPR TM4 and splice variant forms of the PACAP receptor. PACAPR TM4 and PACAPR possess identical intracellular domains, implicated as primary determinants of G protein recognition by rhodopsin-like receptors. However, unlike the PACAPR, PACAPR TM4 does not activate either adenylyl cyclase or phosphoinositide phospholipase C in response to PACAP in either transient or stable expression systems. However, PACAP stimulates increases in [Ca2+]i in cells expressing PACAPR TM4 by activating L-type Ca2+ channels, a response not elicited by stimulation with vasoactive intestinal polypeptide. The signaling phenotype of PACAPR TM4 is characteristic of the PACAP receptor involved in regulation of insulin secretion from pancreatic beta islets, a tissue expressing transcripts for PACAPR TM4 but not for PACAPR or its longer splice variant forms. These findings are consistent with a role of PACAPR TM4 in the physiological control of insulin release by PACAP in beta-islet cells. The finding that PACAPR TM4 has a unique signaling phenotype, although it possesses intracellular domains identical to those of the PACAPR, suggests that receptor-G protein recognition by rhodopsin-like receptors can be determined by sequences other than those located in intracellular receptor domains.
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PMID:Molecular cloning of a novel variant of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor that stimulates calcium influx by activation of L-type calcium channels. 894 80

Reciprocal communication between the immune system and the neuroendocrine system is mediated via a common chemical language of shared ligands and receptors. The neuropeptide substance P (SP) has been implicated as a mediator of immunomodulation. The evidence for substance P receptors on human lymphocytes is, however, controversial. The aims of the present study are to investigate substance P receptor (SPR) expression in human peripheral and mucosal mononuclear cells and to identify cellular sites of expression in human colonic mucosa. Using reverse-transcriptase PCR, we demonstrate that PBMC isolations are negative for SPR mRNA expression, whereas lamina propria mononuclear cell (LPMC) isolations express on average eight SPR mRNA transcripts per cell. In situ hybridization performed on surgically resected colonic tissue confirms the expression of SPR mRNA in LPMC in vivo. SPR mRNA signal was detected in LPMC, lymphoid follicles, and epithelium. The complementary technique of immunohistochemistry gave a similar distribution of SPR expression that colocalized with CD45 immunoreactivity. Dual-fluorochrome flow cytometry revealed SPR expression by CD4, CD45RO, CD45RA, CD8, CD19, and CD14 LPMC subsets, but not PBMC. Our findings suggest that SPR expression is distinctive of human colonic mucosal mononuclear cells and support a direct role for SP in mucosal immunomodulation.
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PMID:Substance P (neurokinin-1) receptor is a marker of human mucosal but not peripheral mononuclear cells: molecular quantitation and localization. 972 16

PRL (prolactin) has been implicated in the proliferation and differentiation of numerous tissues, including the prostate gland. However, the PRL-R (PRL receptor) signal transduction pathway, leading to the stimulation of cell proliferation, remains unclear and has yet to be mapped. The present study was undertaken to develop a clear understanding of the mechanisms involved in this pathway and, in particular, to determine the role of K(+) channels. We used androgen-sensitive prostate cancer (LNCaP) cells whose proliferation is known to be stimulated by PRL. Reverse transcriptase PCR analysis showed that LNCaP cells express a long form of PRL-R, but do not produce its intermediate isoform. Patch-clamp techniques showed that the application of 5 nM PRL increased both the macroscopic K(+) current amplitude and the single K(+)-channel open probability. This single-channel activity increase was reduced by the tyrosine kinase inhibitors genistein, herbimycin A and lavandustine A, thereby indicating that tyrosine kinase phosphorylation is required in PRL-induced K(+) channel stimulation. PRL enhances p59( fyn ) phosphorylation by a factor of 2 after a 10 min application in culture. In addition, where an antip59( fyn ) antibody is present in the patch pipette, PRL no longer increases K(+) current amplitude. Furthermore, the PRL-stimulated proliferation is inhibited by the K(+) channel inhibitors alpha-dendrotoxin and tetraethylammonium. Thus, as K(+) channels are known to be involved in LNCaP cell proliferation, we suggest that K(+) channel modulation by PRL, via p59( fyn ) pathway, is the primary ionic event in PRL signal transduction, triggering cell proliferation.
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PMID:Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation. 1456 46

Changes in intracellular Ca(2+) concentration ([Ca(2+)]i) induced by agonists were simultaneously monitored in rat submandibular acini and ducts using a Ca(2+) imaging system. Substance P (SP) elicited marked increases in [Ca(2+)]i in acini but not in ducts. Carbachol (CCh) increased [Ca(2+)]i in both acini and ducts, but the maximal level was higher in acini than in ducts. In contrast, epinephrine (Epi) also induced an increase in [Ca(2+)]i in acini and ducts, but to a greater extent in ducts than in acini. Isoproterenol (ISO) caused a small but significant increase in [Ca(2+)]i in ducts but not acini. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using total RNA extracted from highly purified acinar and ductal cells showed that substance P receptor mRNA was present in acini at higher levels than in ducts. In contrast, alpha(1a)-adrenoceptor mRNA was more strongly expressed in ducts than in acini. The muscarinic receptors (M(3) and M(5)) and beta-adrenoceptors (beta(1) and beta(2)) were expressed at equivalent levels in both cell types. These results confirm that acini and ducts exhibit significant differences in agonist-induced Ca(2+) responses. Furthermore, substance P- and epinephrine-induced Ca(2+) responses were consistent with receptor mRNA expression in acini and ducts, but carbachol- and isoproterenol-induced [Ca(2+)]i increases were not.
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PMID:Comparison of agonist-induced Ca2+ responses in rat submandibular acini and ducts. 1584 52

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia. Submicroscopic insertion of RARalpha into PML, resulting in PML-RARalpha from derivative chromosome 15, has been rarely reported. Herein, we describe a functional PML-RARalpha transcript from the long arm of derivative chromosome 17 in a patient with microgranular APL. The conventional karyotype showed normal chromosomes 15 and 17. It is interesting that interphase and metaphase fluorescence in situ hybridizations demonstrated a fusion signal on the long arm of one chromosome 17 homolog, with both PML and RARalpha still present on chromosomes 15 and 17, respectively, although the signal on one chromosome 15 was weaker, indicating partial loss of the PML gene. Reverse transcriptase-polymerase chain reaction revealed a transcript corresponding to a break cluster region 3 (bcr3) short form PML-RARalpha. To the best of our knowledge, this is the first report of an APL with a bcr3/short form PML-RARalpha transcript generated from derivative chromosome 17 due to submicroscopic insertion of the PML gene into the RARalpha locus.
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PMID:A bcr3/short form PML-RARalpha transcript in an acute promyelocytic leukemia resulted from a derivative chromosome 17 due to submicroscopic insertion of the PML gene into the RARalpha locus. 1909 67

Carbonic anhydrase (CA) enzymes are expressed in all organs of the mammalian body where they participate in important physiological functions. CA VII is a cytosolic isozyme which may be expressed as two forms according to the recent GenBank data. We designed a present study to express and characterize the human CA VII forms: full-length CA VII and short form (predicted to lack 56 residues from the N-terminus). Reverse transcriptase PCR analysis revealed mRNAs for both CA VII forms in the human brain. These different forms were expressed as recombinant proteins to investigate their biochemical properties. The full-length CA VII was used to raise a polyclonal antiserum in a rabbit, and the antiserum was then employed in western blot analyses and immunohistochemistry of mouse tissues. Data from mass spectrometry and comparative modeling showed that CA VII protein contains a single intramolecular disulfide bridge (Cys-56 to Cys-180) which is lacking in the short form. The computer model suggested distinctly different folding for the different forms. The more exposed structure and the absence of the disulfide bridge in the short form could make this protein more susceptible to degradation. In fact, this was realized in several protein purification efforts in which the short form readily degraded during the experimental procedures. From these results, we conclude that the full-length CA VII is a predominant active form in human brain and also in other tissues. In addition to the brain, CA VII is expressed in several other organs including the stomach, duodenum, colon, liver, and skeletal muscle. The distribution pattern suggests multiple functions for CA VII in different organs.
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PMID:Analysis of a shortened form of human carbonic anhydrase VII expressed in vitro compared to the full-length enzyme. 2049 21

C3d is a sub-fragment of the C3 component of the complement system. Covalent binding of multiple C3ds to antigen reduces the activation threshold of cognate B lymphocytes by one thousand fold through co-ligation of the B cell antigen receptor (BCR) and complement receptor 2 (CR2/CD21). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that, in cattle, four distinct complement receptors are produced from the Cr2 gene by alternative splicing. Cattle express two major variants of the Cr2 gene representing homologues of murine CR1 and CR2, each of which is expressed in both a long and a short form. Expression of CR1 and CR2 was detected in IgM(+) cells from both the spleen and peripheral blood. Additionally, the coding sequence of CD19, the CR2 co-signaling molecule, was determined. CD19 was confirmed to be expressed by IgM(+) cells from the spleen and peripheral blood.
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PMID:Expression of complement receptors 1 (CR1/CD35) and 2 (CR2/CD21), and co-signaling molecule CD19 in cattle. 2298 97

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