Showing papers on "Peptide sequence published in 1986"
TL;DR: A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described.
Abstract: A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described. The predictive accuracy is estimated to be around 75-80% for both prokaryotic and eukaryotic proteins.
4,517 citations
TL;DR: Cloned and sequenced the complete complementary DNA of the oestrogen receptor (ER) present in the breast cancer cell line MCF-7 and found extensive homology between the ER and the erb-A protein of the oncogenic avian erythroblastosis virus.
Abstract: We have cloned and sequenced the complete complementary DNA of the oestrogen receptor (ER) present in the breast cancer cell line MCF-7. The expression of the ER cDNA in HeLa cells produces a protein that has the same relative molecular mass and binds oestradiol with the same affinity as the MCF-7 ER. There is extensive homology between the ER and the erb-A protein of the oncogenic avian erythroblastosis virus.
2,324 citations
TL;DR: The complete primary structure of the human IGF‐I receptor from cloned cDNA is determined and the deduced sequence predicts a 1367 amino acid receptor precursor, including a 30‐residue signal peptide, which is removed during translocation of the nascent polypeptide chain.
Abstract: To identify structural characteristics of the closely related cell surface receptors for insulin and IGF-I that define their distinct physiological roles, we determined the complete primary structure of the human IGF-I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30-residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF-I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg-Lys-Arg-Arg sequence at position 707 of the IGF-I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits.
1,902 citations
TL;DR: A 33-nucleotide sequence, comprised entirely of A and T residues and located in the 3'-untranslated region, is conserved in toto in the murine and human TNF mRNAs.
Abstract: Recently, cDNA sequences have been reported for both human and murine tumor necrosis factor (TNF; cachectin). The coding region of the TNF genes is highly conserved between man and mouse; 80% homology is apparent at the amino acid level. We now observe that a 33-nucleotide sequence, comprised entirely of A and T residues and located in the 3'-untranslated region, is conserved in toto in the murine and human TNF mRNAs. Since the 3'-untranslated region is normally not conserved, we reasoned that this sequence might play a regulatory role. We identified a consensus sequence (TTATTTAT) present in the 3'-untranslated region of both human and mouse TNF mRNAs, as well as the mRNAs encoding human lymphotoxin, human colony stimulating factor, human and mouse interleukin 1, human and rat fibronectin, and most of the sequenced human and mouse interferons. All of these mRNAs, except the lymphotoxin mRNA, lack homology to the TNF mRNAs in the coding region. The consensus sequence is uncommon among mammalian mRNAs in general, but it appears with a frequency greater than chance alone would dictate, suggesting that it may serve a specific regulatory function among the mRNAs in which it is found. It is particularly prevalent among mRNAs encoding proteins related to the inflammatory response.
1,546 citations
01 Jan 1986
TL;DR: The next generation of autonomous vehicles will be able to communicate with each other in a much more efficient and efficient manner than the current generation of vehicles that can communicate solely with the human eye.
Abstract: PERSPECTIVES AND OVERVIEW ............................................................................................................. 32
1,498 citations
TL;DR: Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VzV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.
Abstract: Summary The entire DNA sequence of varicella-zoster virus (VZV) was determined using the M13-dideoxynucleotide technology. The genome is variable in size, but the sequence which was obtained comprises 124884 bp. Analysis of the sequence indicated that the genome contains 70 genes distributed about equally between the two DNA strands. The genes are organized compactly, but regions of overlap between protein-coding regions are not extensive. Many of the genes are arranged in 3′-coterminal families, and at least one is spliced. The discerned organization of VZV genes and that deduced for herpes simplex virus type 1 (HSV-1) from published transcript mapping data indicate that these two members of the Alphaherpesvirinae are very similar in gene layout. Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VZV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.
1,451 citations
TL;DR: The RGD sequence as a basic unit of a widespread cellular recognition system is established and the same peptides also inhibit the attachment of fibroblasts to a number of other proteins, including vitronectin.
1,363 citations
TL;DR: Cloning of the gene and cDNA for the mammalian β2AR indicates significant amino-acid homology with bovine rhodopin and suggests that, like rhodopsin7, βAR possesses multiple membrane-spanning regions.
Abstract: The adenylate cyclase system, which consists of a catalytic moiety and regulatory guanine nucleotide-binding proteins, provides the effector mechanism for the intracellular actions of many hormones and drugs. The tissue specificity of the system is determined by the particular receptors that a cell expresses. Of the many receptors known to modulate adenylate cyclase activity, the best characterized and one of the most pharmacologically important is the beta-adrenergic receptor (beta AR). The pharmacologically distinguishable subtypes of the beta-adrenergic receptor, beta 1 and beta 2 receptors, stimulate adenylate cyclase on binding specific catecholamines. Recently, the avian erythrocyte beta 1, the amphibian erythrocyte beta 2 and the mammalian lung beta 2 receptors have been purified to homogeneity and demonstrated to retain binding activity in detergent-solubilized form. Moreover, the beta-adrenergic receptor has been reconstituted with the other components of the adenylate cyclase system in vitro, thus making this hormone receptor particularly attractive for studies of the mechanism of receptor action. This situation is in contrast to that for the receptors for growth factors and insulin, where the primary biochemical effectors of receptor action are unknown. Here, we report the cloning of the gene and cDNA for the mammalian beta 2AR. Analysis of the amino-acid sequence predicted for the beta AR indicates significant amino-acid homology with bovine rhodopsin and suggests that, like rhodopsin, beta AR possesses multiple membrane-spanning regions.
1,225 citations
TL;DR: The purpose today is to describe the chemical synthesis of peptides and proteins and to discuss the use of the synthetic approach to answer various biological questions.
Abstract: The proteins, as the Greek root of their name implies, are of first rank in living systems, and their smaller relatives, the peptides, have now also been discovered to have important roles in biology. Among their members are many of the hormones, releasing factors, growth factors, ion carriers, antibiotics, toxins, and neuropeptides. My purpose today is to describe the chemical synthesis of peptides and proteins and to discuss the use of the synthetic approach to answer various biological questions. The story begins with Emil Fischer (1) at the turn of this century when he synthesized the first peptide and coined the name. The general chemical requirements were to block the carboxyl group of one amino acid and the amino group of the second amino acid. Then, by activation of the free carboxyl group the peptide bond could be formed, and selective removal of the two protecting groups would lead to the free dipeptide. Fischer himself was never able to find a suitable reversible blocking group for the amine function, but his former student Max Bergmann, with Zervas, was successful (2). Their design of the carbobenzoxy group ushered in a new era. When I began working on the synthesis of peptides many years later this same general scheme was universally in use and was very effective, having led, for example, to the first synthesis of a peptide hormone by Du Vigneaud in 1953 (3). It soon became clear to me, however, that such syntheses were difficult and time consuming and that a new approach was needed if large numbers of peptides were required or if larger and more complex peptides were to be made.
1,216 citations
TL;DR: A neu complementary DNA clone isolated from a cell line transformed by this oncogene is decribed and suggests strongly that the neu gene encodes the receptor for an as yet unidentified growth factor.
Abstract: The neu oncogene is repeatedly activated in neuro- and glioblastomas derived by transplacental mutagenesis of the BDIX strain of rat with ethylnitrosourea. Foci induced by the DNAs from such tumours on NIH 3T3 cells contain the neu oncogene and an associated phosphoprotein of relative molecular mass 185,000 (p185). Previous work has shown that the neu gene is related to, but distinct from, the gene encoding the EGF receptor (c-erb-B). Here we describe a neu complementary DNA clone isolated from a cell line transformed by this oncogene; the clone has biological activity in a focus-forming assay. The nucleotide sequence of this clone predicts a 1,260-amino-acid transmembrane protein product similar in overall structure to the EGF receptor. We found that 50% of the predicted amino acids of neu and the EGF receptor are identical; greater than 80% of the amino acids in the tyrosine kinase domain are identical. Our results suggest strongly that the neu gene encodes the receptor for an as yet unidentified growth factor.
1,166 citations
TL;DR: An amino acid sequence “fingerprint” has been derived that can be used to test if a particular sequence will fold into aβαβ-unit with ADP-binding properties, which is in fact a set of 11 rules describing the type of amino acid that should occur at a specific position in a peptide fragment.
TL;DR: A comparison of the bovine and human MIS proteins reveals a highly conserved C-terminal domain that shows marked homology with human transforming growth factor-beta and the beta chain of porcine inhibin.
TL;DR: The results show that the Arg-Gly-Asp sequence also confers cell-binding properties on bone-specific sialoprotein, and the name "osteopontin" is proposed for this protein to better reflect the potential function of bone sIALoprotein.
Abstract: The primary structure of a bone-specific sialoprotein was deduced from cloned cDNA. One of the cDNA clones isolated from a rat osteosarcoma (ROS 17/2.8) phage lambda gt11 library had a 1473-base-pair-long insert that encoded a protein with 317 amino acid residues. This cDNA clone appears to represent the complete coding region of sialoprotein mRNA, including a putative AUG initiation codon and a signal peptide sequence. The amino acid sequence deduced from the cDNA contains several Ser-Xaa-Glu sequences, possibly representing attachment points for O-glycosidically linked oligosaccharides and one Asn-Xaa-Ser sequence representing a likely site for the N-glycosidically linked oligosaccharide. An interesting observation is the Gly-Arg-Gly-Asp-Ser sequence, which is identical to the cell-binding sequence identified in fibronectin. The presence of this sequence prompted us to investigate the cell-binding properties of sialoprotein. The ROS 17/2.8 cells attached and attained a spread morphology on surfaces coated with sialoprotein. We could demonstrate that synthetic Arg-Gly-Asp-containing peptides efficiently inhibited the attachment of cells to sialoprotein-coated substrates. The results show that the Arg-Gly-Asp sequence also confers cell-binding properties on bone-specific sialoprotein. To better reflect the potential function of bone sialoprotein--we propose the name "osteopontin" for this protein.
TL;DR: The complete nucleotide and primary structure of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented and strong homology suggests that a highly conserved functional unit involved in membrane transport is present in the mdr polypeptide.
TL;DR: The name integrin is proposed for this protein complex to denote its role as an integral membrane complex involved in the transmembrane association between the extracellular matrix and the cytoskeleton.
TL;DR: The complete amino acid sequence of bovine protein kinase C was determined, revealing a domain structure that shows substantial homology, but not identity, to sequences of other protein kinases.
Abstract: Protein kinase C, the major phorbol ester receptor, was purified from bovine brain and through the use of oligonucleotide probes based on partial amino acid sequence, complementary DNA clones were derived from bovine brain complementary DNA libraries. Thus, the complete amino acid sequence of bovine protein kinase C was determined, revealing a domain structure. At the amino terminal is a cysteine-rich domain with an internal duplication; a putative calcium-binding domain follows, and there is at the carboxyl terminal a domain that shows substantial homology, but not identity, to sequences of other protein kinase.
TL;DR: The most prominent structural feature of both lamins is an α-helical region of repeating heptads of amino acids that shows striking homology with the entire family of cytoplasmic intermediate filament proteins, suggesting that the nuclear envelope is made up of a network of coiled-coil polymers.
Abstract: The A, B and C lamins are the major proteins of the nuclear envelope. The complete nucleotide sequence of the coding region of the A and C lamins shows that these proteins are identical except for their carboxy termini. The most prominent structural feature of both lamins is an alpha-helical region of repeating heptads of amino acids that shows striking homology with the entire family of cytoplasmic intermediate filament proteins. These features suggest that the nuclear envelope is made up of a network of coiled-coil polymers.
TL;DR: A cDNA clone encoding a novel hematopoietic growth factor activity produced by a gibbon T cell line has been identified using a mammalian cell expression cloning system and the recombinant gibbon IL-3 protein proved to have multipotent colony stimulating activity when tested with normal human bone marrow cells, proving that this primate hematoietin is not only structurally but also functionally related to murine IL- 3.
TL;DR: A transport mechanism is proposed in which Ca2+ binds to negatively charged groups on amphipathic stalk sectors, becoming occluded during enzyme phosphorylation by bound ATP.
TL;DR: A chicken oviduct cDNA clone containing the complete open reading frame of the oestrogen receptor (ER) has been isolated and sequenced, indicating that c‐erbA, the cellular counterpart of v‐erbB, belongs to a multigene family of transcriptional regulatory proteins which bind steroid‐related ligands.
Abstract: A chicken oviduct cDNA clone containing the complete open reading frame of the oestrogen receptor (ER) has been isolated and sequenced. The mol. wt of the predicted 589-amino acid protein is approximately 66 kd which is very close to that of the human ER. Comparison of the human and chicken amino acid sequences shows that 80% of their amino acids are identical. There are three highly conserved regions; the second and third of which probably represent the DNA- and hormone-binding domains of the receptor. The putative DNA-binding domain is characterised by its high cysteine and basic amino acid content, and the hormone-binding domain by its overall hydrophobicity. These two domains of homology are also present in the human glucocorticoid receptor (GR) and the product of the avian erythroblastosis virus (AEV) gene, v-erbA, indicating that c-erbA, the cellular counterpart of v-erbA, belongs to a multigene family of transcriptional regulatory proteins which bind steroid-related ligands. The first highly conserved ER region is not present in the truncated v-erbA gene, but shares some homology with the N-terminal end of the GR. The function of the v-erbA gene product is discussed in relation to its homology with the ER and GR sequences.
TL;DR: It is concluded that diversification of preproglucagon gene expression occurs at the level of cell-specific post-translational processing.
TL;DR: The amino acid sequences deduced from cDNA clones of human lamins A and lamin C show identity between these two lamins except for an extra 9.0-kDa carboxyl-terminal tail that is present only in lamin A.
Abstract: The amino acid sequences deduced from cDNA clones of human lamin A and lamin C show identity between these two lamins except for an extra 9.0-kDa carboxyl-terminal tail that is present only in lamin A. Both lamins A and C contain an alpha-helical domain of approximately 360 residues that shows striking homology to a corresponding alpha-helical rod domain that is the structural hallmark of all intermediate filament proteins. However, the lamin alpha-helical domain is 14% larger than that of the intermediate filament proteins. In addition to the extensive homology to intermediate filament proteins as reported [McKeon, F., Kirschner, M. & Caput, D. (1986) Nature (London) 319, 463-468], a different 82-amino acid residue stretch at the carboxyl terminus of lamin A has been deduced and verified by amino acid sequencing. This region contains sequence homology to amino- and carboxylterminal domains of type I and type II epidermal keratins. Implications of the presence of these and other domains in lamins A and C for the assembly of the nuclear lamina are discussed.
TL;DR: The cloned receptor protein activates its corresponding enhancers, restoring to the receptor-deficient cells the full capacity for regulated enhancement.
TL;DR: The 49-residue peptide strongly inhibits glucose-induced insulin release from the isolated perfused pancreas and was therefore named pancreastatin and may be important in the regulation of insulin secretion and in the pathogenesis and treatment of diabetes mellitus.
Abstract: In mammalian tissues the C-terminal amide structure has been found to occur only in neuroactive or hormonally-active peptides. About half known neuropeptide and peptide hormones have this unique chemical feature. Using a chemical detection method, a search for previously unknown peptides that possess the C-terminal amide structure in extracts of brain and intestine was carried out and a number of novel neuropeptides and hormonal peptides, designated neuropeptide Y, PHI, peptide YY, galanin and neuropeptide K were isolated. We recently performed a similar search in porcine pancreas and found a high concentration of a peptide having a glycine amide at its C-terminus. Here we report the isolation, primary structure and biological activity of this novel peptide. The 49-residue peptide strongly inhibits glucose-induced insulin release from the isolated perfused pancreas and was therefore named pancreastatin. It may be important in the regulation of insulin secretion and in the pathogenesis and treatment of diabetes mellitus.
TL;DR: A lysine-rich sequence that may function as a movable, ion-selective gate during cation binding and occlusion and several amino acid sequence variations that appear to explain some of the well-known species and tissue differences in cardiac glycoside sensitivity are identified.
Abstract: Rat brain and kidney cDNA libraries were constructed and screened with a cDNA insert corresponding to the mRNA for the sheep kidney Na+,K+-ATPase catalytic subunit. The alpha-subunit cDNAs isolated from the kidney library were derived from a single class of messenger RNA, and the brain cDNAs were derived from three classes of messenger RNA. The most abundant brain cDNA, which spans 5.1 kilobases, encodes the alpha(+) form of the enzyme. The second most abundant brain cDNA, which spans 3.65 kilobases, is identical with that of the kidney form and therefore encodes the alpha isoform. The third class of cDNA, which spans 3.55 kilobases, was present at low abundance and encodes an isoform of the alpha-subunit, designated alpha III, which has not been identified previously. The complete nucleotide sequence and deduced amino acid sequence for each of the brain and kidney cDNAs have been determined. In addition, we have identified a lysine-rich sequence that may function as a movable, ion-selective gate during cation binding and occlusion and have also identified several amino acid sequence variations that appear to explain some of the well-known species and tissue differences in cardiac glycoside sensitivity.
TL;DR: A T-cell derived lymphokine was identified by its ability to support the growth of a subset of B-cell hybridomas as mentioned in this paper, which represented a major proportion of rat-mouse hybridomas.
Abstract: A T-cell-derived lymphokine was identified by its ability to support the growth of a subset of B-cell hybridomas. Hybrids that failed to survive in the absence of this molecule represented a major proportion of rat-mouse hybridomas but were very rare among mouse-mouse B-cell hybrids. Stable factor-dependent B-cell hybridomas were used to monitor the purification of the growth factor from the supernatant of a clonotypically stimulated mouse helper T-cell clone. Sequential fractionation using gel filtration, anion-exchange chromatography, and reversed-phase HPLC resolved the factor from other B-cell growth factors and yielded a single-chain protein characterized by a major charge (pI = 5-7) and molecular mass (22- to 29-kDa) heterogeneity, probably due to variations in glycosylation. The NH2-terminal amino acid sequence of this protein, which is active on B-cell hybridomas in the 0.1 pM range, showed no significant homology with that of known lymphokines. Because the purified factor also supported the growth and survival in vitro of murine plasmacytomas (to be published elsewhere), it was provisionally designated interleukin-HP1 (where H stands for hybridoma and P stands for plasmacytoma).
TL;DR: The complete amino acids sequence of human ECGF was deduced from the nucleic acid sequence of these clones; it encompasses all the well-characterized acidic endothelial cell polypeptide mitogens described by several laboratories.
Abstract: Several of the endothelial cell polypeptide mitogens that have been described probably play a role in blood vessel homeostasis. Two overlapping complementary DNA clones encoding human endothelial cell growth factor (ECGF) were isolated from a human brain stem complementary DNA library. Southern blot analysis suggested that there is a single copy of the ECGF gene and that it maps to human chromosome 5 at bands 5q31.3 to 33.2 A 4.8-kilobase messenger RNA was present in human brain stem messenger RNA. The complete amino acid sequence of human ECGF was deduced from the nucleic acid sequence of these clones; it encompasses all the well-characterized acidic endothelial cell polypeptide mitogens described by several laboratories. The ECGF-encoding open reading frame is flanked by translation stop codons and provides no signal peptide or internal hydrophobic domain for the secretion of ECGF. This property is shared by human interleukin-1, which is approximately 30 percent homologous to ECGF.
TL;DR: A new acute transforming feline retrovirus, the Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), has been isolated from a feline fibrosarcoma.
Abstract: A new acute transforming feline retrovirus, the Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), has been isolated from a feline fibrosarcoma The viral genome of HZ4-FeSV contains a new oncogene designated v-kit, has the structure 5' delta gag-kit-delta pol-delta env 3' and specifies a gag-kit polyprotein of relative molecular mass 80,000 The predicted kit amino-acid sequence displays partial homology with tyrosine-specific protein kinase oncogenes HZ4-FeSV appears to have been generated by transduction of feline c-kit sequences with feline leukaemia virus
TL;DR: Southern blot analysis of human genomic DNA and mapping of the cloned gene shows that there is only one basic FGF gene, and all of the basic, heparin‐binding endothelial cell mitogens of similar amino acid composition that have been described must be products of this single gene.
Abstract: Clones encoding the angiogenic endothelial cell mitogen, basic fibroblast growth factor (FGF), have been isolated from human cDNA libraries made from kidney, fetal heart, fetal liver, term placenta, and a breast carcinoma. Basic FGF cDNA clones are present in these libraries at very low levels when compared to the quantity of the growth factor in the tissues. This observation, combined with the fact that several of the clones represent unspliced transcripts, suggests that cytoplasmic basic FGF mRNA is unstable and that the protein is stored in tissues. The amino acid sequence of human basic FGF, deduced from the sequence of these cDNAs and from genomic clones, is 99% homologous to that of bovine basic FGF, implying a strong selection pressure for maintenance of function and structure. As with the bovine factor, human basic FGF does not appear to have a signal peptide sequence. Southern blot analysis of human genomic DNA and mapping of the cloned gene shows that there is only one basic FGF gene. All of the basic, heparin-binding endothelial cell mitogens of similar amino acid composition that have been described must therefore be products of this single gene.
TL;DR: As an important new reagent for studying the cAMP-dependent protein kinase, a 20-residue peptide has been synthesized that corresponds to the active site of the skeletal muscle inhibitor protein.