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Biomedical subjects

T B Shows

Publications and source records attributed to T B Shows.

At least 181 records · Page 10Linked to original sources
PubMed1990

Identification and chromosomal mapping of new human tyrosine kinase genes.

To identify novel protein tyrosine kinase (PTK) genes expressed in human lymphoid cells, we have screened B- and T-cell cDNA libraries at low stringency using a c-fms tyrosine kinase domain probe. Three new PTK genes were identified, based on the presence of conserved amino acid sequence motifs characteristic of the catalytic domain of tyrosine kinases. Of these three genes, one (tyk1) appears to be the human homologue of a previously cloned murine gene (ltk), which has been reported to encode a tyrosine kinase with a unique structure; while the second gene, tyk2 cannot be clearly assigned to any of the known PTK subfamilies, and therefore may be the prototype of a new PTK gene subfamily. The third gene (tyk3/fer) has been very recently cloned by others; we present additional characterization in this report. We have performed Northern blots to establish the size of the mRNA encoded for by these genes, and to confirm their expression in lymphoid cells. Finally, we have determined the chromosomal location of all three genes by analyzing human-mouse somatic cell hybrids.

Amino Acid Sequence↗
PubMed1989

cDNA cloning and chromosomal assignment of the gene encoding endothelin 3.

The vasoactive peptide endothelin 1 (ET1) is encoded by a well characterized gene located on human chromosome 6. Recently, two human genomic fragments were isolated which potentially encode related vasoconstrictor peptides, endothelin 2 (ET2) and endothelin 3 (ET3) (Inoue, A., Yanagisawa, M., Kimura, S., Kasuya, Y., Miyauchi, T., Goto, K., and Masaki, T. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 2863-2867). Inoue et al. were unable to detect transcripts of the ET2 and ET3 genes and observed ET1 gene expression exclusively in endothelial cells. In this study, we document transcription of the ET3 gene by isolating from a hypothalamic cDNA library DNA clones complementary to human ET3 mRNA. ET3 mRNA encodes a 238-amino acid precursor that includes ET3 and a 15-amino acid homologous segment, the ET3-like sequence. On the basis of DNA isolated from human-mouse somatic hybrid cell lines, we assigned the ET3 gene to human chromosome 20. The ET3 and ET1 genes are, therefore, not genetically linked. RNA blot hybridization with restriction fragments derived from cDNAs revealed that the ET3 and ET1 genes are both expressed in lung, pancreas, and spleen. Cultured endothelial cells and cardiac tissues express the ET1 but not the ET3 gene. Observations that genes encoding endothelin-related peptides are expressed in a variety of human tissues suggest that these peptides may participate in complex vasoregulatory mechanisms.

Amino Acid Sequence↗
PubMed1989

The human cystatin C gene (CST3) is a member of the cystatin gene family which is localized on chromosome 20.

The fourth gene from the human cystatin gene family of salivary-type cysteine-proteinase inhibitors has been isolated and partially characterized by DNA analysis. The gene, which we name CST3, codes for human cystatin C, and has the same organization as the CST1 gene for cystatin SN and the CST2 gene for cystatin SA. Southern analysis of EcoR I digested DNAs from 32 independent somatic cell hybrid clones hybridized to a probe from CST1 demonstrated that all members of the cystatin gene family segregate with human chromosome 20. These results indicate that the genes for salivary-type cystatins and cystatin C are members of a multigene family--the cystatin gene family.

Amino Acid Sequence↗
PubMed1989

Structural organization and chromosomal assignment of the gene encoding endothelin.

Endothelin is a 21-amino acid vasoconstrictor synthesized and secreted by vascular endothelial cells. The human peptide is derived from a 212-amino acid precursor, preproendothelin. A nearly full length clone containing DNA complementary to human preproendothelin mRNA was isolated, and its nucleotide sequence was determined. Using this cDNA as a probe, the genomic organization of the human endothelin gene was determined and the promoter region delineated. The gene contains five exons and four intervening sequences. Nucleotide sequences encoding endothelin are contained within the second exon, and the third exon specifies a portion of preproendothelin that is homologous to endothelin. The second and third exons may represent descendants of a common progenitor exon. The 3'-untranslated portion of the gene contains a 250-base pair region that is highly conserved between human and porcine genomes and may have an important role in endothelin mRNA stability. On the basis of DNA isolated from human-mouse somatic hybrid cell lines, the endothelin gene was assigned to human chromosome 6.

Amino Acid Sequence↗
PubMed1989

Long-range restriction map around 11p13 aniridia locus.

Using two random DNA markers, and pulsed field gel electrophoresis, a 1.5-Mb physical map surrounding the 11p13 aniridia locus (AN2) has been assembled. The map was constructed using a combination of single- and double-restriction digests on DNA from normal controls and a patient transmitting familial aniridia. The aniridia patient has a chromosome translocation and the two DNA markers flank the breakpoint. This 11p13 breakpoint lies no further than 100 kb from the DNA marker 1104 (D11S95), located on the centromeric side of the breakpoint. Two CpG islands, separated by 550 kb and flanking the translocation, suggest an upper limit to the size of the gene.

Aniridia↗
PubMed1989

Genomic organization and chromosomal assignment for a serine protease gene (CSPB) expressed by human cytotoxic lymphocytes.

The human cytotoxic serine protease ("granzyme") B gene has been isolated and sequenced. The gene is approximately 3500 bp in length and consists of five exons and four intervening introns. Its organization therefore conforms closely to that of the previously cloned serine protease genes which are expressed in mouse cytotoxic lymphocytes and rat mast cells. The 5' upstream region is characterized by an atypical "TATA"-like transcriptional promoter and by a stretch of nucleotides bearing similarity to an enhancer core sequence believed to be requisite for the tissue-specific expression of serine protease genes in the exocrine pancreas. It has previously been demonstrated that mRNA transcripts from the human serine protease B gene are heterogeneous in size, due to frequent faulty intron/exon splicing. Two cryptic splice sites, which are used to generate these aberrant mRNA transcripts, have been identified. Using DNA blot analysis of a panel of human-rodent somatic cell lines, the human serine protease B gene has been localized to chromosome 14.

Amino Acid Sequence↗
PubMed1989

Assignment of the human collagen alpha 1 (XIII) chain gene (COL13A1) to the q22 region of chromosome 10.

Type XIII collagen is a recently described collagen that resembles in structure the short-chain collagens of types IX, X, and XII. Unlike any other collagen, the type XIII is found in several different forms generated through alternative splicing. A 2.0-kb genomic fragment from the human alpha 1 (XIII) collagen gene was isolated and shown by DNA sequencing to contain exon 12 as counted from the 3' end. This fragment was used as a probe to localize the gene. The gene (COL13A1) was assigned to chromosome 10 by hybridization of the probe to DNA isolated from a panel of human-mouse somatic cell hybrids containing different human chromosomes. Furthermore, the gene was mapped to the q22 region by in situ hybridization to metaphase chromosomes.

Amino Acid Sequence↗
PubMed1989

Mapping and characterization of an X-linked processed gene related to MYCL1.

A DNA sequence with homology to the myc family of proto-oncogenes has been characterized and found to be a processed gene related to L-MYC (MYCL1). This processed gene (MYCL2) was isolated by cross-hybridization to an oligonucleotide probe synthesized from the C-MYC (MYC) sequence in a highly conserved region of the myc gene family. Sequence analysis of MYCL2 revealed an open reading frame of 1194 bp with no intervening sequences and strong homology to the recently published DNA sequence of MYCL1. Southern and Northern blot analyses of DNAs and RNAs from small cell lung carcinomas confirmed its MYCL1 homology. Mapping of MYCL2 by somatic cell hybrids places this sequence on the long arm of the X chromosome in bands q22----q28.

Animals↗
PubMed1989

The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2.

The gene for the human mineralocorticoid receptor (MLR) was previously localized to chromosome 4. Here, we have localized this gene to 4q31.2 by in situ hybridization. This precise mapping of MLR will assist in the linkage analysis and genetic characterization of pseudohypoaldosteronism, an autosomal recessive disorder which likely results from a defect in the MLR gene.

Animals↗
PubMed1989

Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma.

Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development.

Adenoma↗
PubMed1989

Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history.

The gene-encoding human islet amyloid polypeptide (hIAPP), a recently discovered 37 amino acid hormone-like polypeptide which is expressed in the insulin-producing beta-cells of the endocrine pancreas, has been isolated and characterized. The coding region of the gene is interrupted in the 5'-untranslated region and NH2-terminal propeptide by introns of 330 and 4808 base pairs (bp), respectively. Exon 1 (104 bp) encodes most of the 5'-untranslated region of the mRNA; exon 2 (95 bp) encodes 15 nucleotides of 5'-untranslated region, the putative 22 amino acid signal peptide and five residues of the NH2-terminal propeptide; exon 3 (1246 bp) encodes the remainder of the NH2-terminal propeptide (residues 6-9), the IAPP moiety and its processing signals and the 16 amino acid COOH-terminal propeptide, as well as the 3'-untranslated region of the mRNA (1059 bp). Analysis of the nucleotide and predicted amino acid sequence of intron 2 of the hIAPP gene did not reveal any homology with the structurally related calcitonin/calcitonin-gene-related peptide genes and indicated that, in contrast to these latter genes, the hIAPP gene apparently gives rise to only a single hormonal product. The transcriptional initiation site was identified about 28 bp downstream from a TATAA sequence. The hIAPP gene was localized to the p12.3 region of chromosome 12.

Amino Acid Sequence↗
PubMed1989

Gastric inhibitory polypeptide: structure and chromosomal localization of the human gene.

Gastric inhibitory polypeptide (GIP) is a 42-amino-acid hormone which may have a role in the regulation of insulin secretion. The characterization of cDNA clones encoding this hormone indicates that it is derived by proteolytic processing of a 153-amino-acid precursor. The human gene coding for the human GIP precursor spans approximately 10 kilobase pairs and consists of six exons. Similar to genes encoding other members of the glucagon superfamily, each exon appears to encode a distinct region of the GIP precursor or its mRNA. The promoter region of the human GIP gene contains potential binding sites for a number of transcriptional factors including Sp 1, AP-1, and AP-2. The human GIP gene has been assigned to chromosome 17q21.3----q22.

Base Sequence↗
PubMed1989

Polymorphic human insulin-responsive glucose-transporter gene on chromosome 17p13.

Glucose uptake by heart, skeletal muscle, and adipose tissue is acutely regulated by insulin, which stimulates facilitative glucose transport, at least in part, by promoting the translocation of transporters from an intracellular pool to the plasma membrane. cDNAs encoding the major human insulin-responsive glucose transporter have been isolated and indicate that the insulin-responsive glucose transporter expressed by heart, skeletal muscle, and adipose tissue is a 509-amino acid protein having 65.3, 54.3, and 57.5% identity with the erythrocyte/HepG2, liver, and fetal muscle glucose transporters, respectively. The gene encoding the insulin-responsive glucose transporter (designated GLUT4) was mapped to the p11----p13 region of the short arm of human chromosome 17 by analyzing its segregation in a panel of reduced human-mouse somatic cell hybrids. In situ hybridization to prometaphase chromosomes indicated that GLUT4 was in band p13. A common two-allele restriction-fragment-length polymorphism (RFLP) was identified with Kpn I, and linkage of this RFLP to other polymorphic DNA markers in this region of chromosome 17 provides a set of probes that will be useful for examining the role of this gene in the pathogenesis of diabetes mellitus.

Chromosome Mapping↗
PubMed1989

The gene for the human mast cell high-affinity IgE receptor alpha chain: chromosomal localization to Iq21-q23 and RFLP analysis.

We have used a cDNA probe for the human IgE receptor alpha chain to determine the chromosomal location for the human gene. A combination of Southern blot analysis of panels of somatic-cell hybrid DNAs and chromosomal in situ hybridization has localized the gene to the long arm of chromosome 1 at q21-q23. With this cDNA probe, we have also identified an RsaI RFLP which is inherited in a Mendelian fashion. This polymorphic marker on chromosome 1 should be valuable for studies directed at the identification both of diseases involving the IgE receptor alpha chain and of genetic factors affecting the allergic response.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Evidence for a family of human glucose transporter-like proteins. Sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues.

Complementary DNA clones encoding a glucose transporter-like protein have been isolated from a human fetal skeletal muscle cDNA library. The 496-amino acid fetal muscle glucose transporter-like protein has 64.4 and 51.6% identity with the previously described human erythrocyte/HepG2 and liver glucose transporter sequences, respectively. RNA blotting studies indicate that transcripts encoding this glucose transporter-like protein are present in most tissues, although their relative abundance varies. The gene encoding this protein has been localized to human chromosome 12p13.3. The identification and characterization of a third human glucose transporter-related protein suggests that there is a family of proteins having similar sequences and structures which are involved in nutrient transport by mammalian cells.

Amino Acid Sequence↗
PubMed1988

Two anonymous DNA segments distinguish the Wilms' tumor and aniridia loci.

The association of Wilms' tumor with aniridia (the WAGR complex) in children with 11p13 chromosomal abnormalities has been established, but the paucity of molecular probes in 11p13 has hampered identification of the responsible genes. Two new anonymous DNA segments have been identified that map to the WAGR region of 11p13. Both DNA probes identify a cytologically undetectable deletion associated with a balanced chromosome translocation inherited by a patient with familial aniridia, but not Wilms' tumor. The same two DNA segments are also included in the distal p13-p14.1 deletion of another patient, who has aniridia, Wilms' tumor, and hypogonadism, but they are not included in the p12-p13 deletion of a third patient, who does not have aniridia but has had a Wilms' tumor. The discovery of this aniridia deletion and these two DNA segments that physically separate the Wilms' tumor and aniridia loci should facilitate identification of the genes in the WAGR locus, beginning with the aniridia gene.

Animals↗
PubMed1988

A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization.

Egr-1 is an early growth response gene that displays fos-like induction kinetics in fibroblasts, epithelial cells, and lymphocytes following mitogenic stimulation. Sequence analysis of murine Egr-1 cDNA predicts a protein with three DNA binding zinc fingers. The human EGR1 gene maps to chromosome 5 (bands 5q23-31). Egr-1 mRNA increases dramatically during cardiac and neural cell differentiation, and following membrane depolarization both in vitro and in vivo. Thus, Egr-1 and c-fos are often coregulated with strikingly similar kinetics. These results, in conjunction with the Egr-1 primary structure, suggest that Egr-1 may function as a transcriptional regulator in diverse biological processes.

Amino Acid Sequence↗