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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hypotheses have been presented to explain the grossly biphasic oxygen release kinetics observed when hemoglobins are studied with the oxygen pulse technique [Gibson (1973) Proc. Nat. Acad. Sci. USA 70, 1-4]. Hypothesis I suggests that the two phases result from cooperativity, with the fast phase being oxygen release from the low affinity (T) state and the slow phase being oxygen release from molecules that have switched to the high affinity (R) state. Hypothesis II suggests that the biphasic curves are due to a large (factor of 20-30) difference in oxygen release from the two types of subunits within deoxyhemoglobin. In order to experimentally discriminate between these two hypotheses, we reinvestigated the oxygen pulse reaction for hemoglobin Kansas (alpha2 beta2 102 Asn leads to Thr) in the absence and presence of inositol hexaphosphate, since recent high resolution nuclear magnetic resonance studies have shown that this allosteric cofactor stabilizes hemoglobin Kansas in T even when fully liganded [Ogawa, Mayer, and Shulman (1972) Biochem. Biophys. Res. Commun. 49, 1485-1491]. The results of these studies clearly favor hypothesis I over hypothesis II as being the correct interpretation for the oxygen pulse results. However, we have found evidence that suggests that oxygen release and binding in T are surprisingly faster than previously observed. Furthermore, within T, there is some spectral and kinetic heterogeneity for oxygen release from adult hemoglobin and hemoglobin Kansas. The magnitude of this kinetic heterogeneity in T appears to be about the same as that seen in the high affinity, R, state. The exchange of hypothesis II for hypothesis I more strongly favors views of cooperative oxygen binding involving both types of subunits, as required if the allosteric model of Monod, Wyman, and Changeux [(1965) J. Mol. Biol. 12, 88-118] is considered operative.
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PMID:Magnitude of subunit inequivalence for oxygen release from hemoglobin: reinvestigation of the oxygen-pulse experiment. 106 81

Two mutations restricting the leakiness of an amber mutant are described. They were selected without the use of streptomycin: one maps in the strA region (at 64 minutes of the current E. coli chromosomal map) but is streptomycin sensitive and the other in the threonine region (at the origin of the map), 23% cotransducible with threonine by P1.
Mol Gen Genet 1975
PMID:A new gene for ribosomal restriction in Escherichia coli. 110 Oct 29

Cationic amino acids, arginine and lysine partition differentially from water into aqueous micellar sodium dodecanoate. Conversely, partitioning of serine, glycine, aspartic acid, glutamic acid, threonine, alanine, proline, valine, leucine, phenylalanine and isoleucine do not vary appreciably. Partitioning from neat hexane into dodecylammonium propionate trapped water in hexane is, however, dependent upon both electrostatic and hydrophobic interactions. These results imply that the interior of dedecylammonium propionate aggregates is negatively charged and is capable of hydrogen bonding in addition to providing a hydrophobic enviroment. The solubilities of amino acids in neat hexane substantiate the previously derived amino acid hydrophobicity scale. Relevance of partitioning in these systems to the postulated selective amino acid compartmentalization is discussed.
J Mol Evol 1975 Nov 04
PMID:Compartmentalization of amino acids in surfactant aggregates. Partitioning between water and aqueous micellar sodium deodecanoate and between hexane and dodecylammonium propionate trapped water in hexane. 120 27

A model is proposed for the structure of stereospecific sites in regulatory proteins. On its basis a possible code is suggested that governs the binding of regulatory proteins at specific control sites on DNA. Stereospecific sites of regulatory proteins are assumed to contain pairs of antiparallel polypeptide chain segments which form a right-hand twisted antiparallel beta-sheet, with single-stranded regions at the ends of the beta-structure. The model predicts that binding reaction between a regulatory protein and double-helical DNA is a cooperative phenomenon and is accompanied by significant structural alteration at the stereospecific site of the protein. Half of hydrogen bonds normally existing in beta-structure are broken upon complex formation with DNA and a new set of hydrogen bonds is formed between polypeptide amide groups and DNA base pairs. In a stereospecific site, one chain (t-chain) is attached through hydrogen bonds to the carbonyl oxygens of pyramides and N3 adenines lying in one DNA strand, while the second polypeptide chain (g chain) is hydrogen bonded to the 2-amino groups of guanine residues lying in the opposite DNA strand. The amide groups serve as specific reaction sites being hydrogen bond acceptors in g-chain and hydrogen bond donors in t-chain. The single-stranded portions of t- and g-chains lying in neighbouring subunits of regulatory protein interact with each other forming deformed beta-sheets. The recognition of regulatory sequences by proteins is based on the structural complementarity between stereospecific sites of regulatory proteins and base pairs sequences at the control sites. An essential feature of these sequences is the asymmetrical distribution of guanine residues between the two DNA strands. The code predicts that there are six fundamental amino acid residues (serine, threonine, asparagine, histidine, glutamine and cysteine) whose sequence in stereospecific site determines the base pair sequence to which a given regulatory protein would bind preferentially. The code states a correspondence between four amino acid residues at the stereospecific site of regulatory protein with the two residues being in t- and g-segments, respectively, and AT(GC) base pair at the control site. It is thus possible to determine which amino acid residues in the repressor and which base pairs in the operator DNA are involved in specific interactions with each other, as exemplified by lac repressor binding to lac operator.
Mol Biol (Mosk)
PMID:[A code governing specific binding of regulatory proteins to DNA and structure of stereospecific sites of regulatory proteins]. 121 4

A possible code is suggested that describes a correspondence between amino acid sequences in stereospecific sites of regulatory proteins and nucleotide sequences at the control sites on DNA. Stereospecific sites of regulatory proteins are assumed to contain pairs of antiparallel polypeptide chain segments which form a right-hand twisted antiparallel beta-sheet with single-stranded regions at the ends of the beta-structure. The binding reaction between regulatory protein and double-helical DNA is accompanied by significant structural alterations at stereospecific sites of the protein and DNA. Half of the hydrogen bonds normally existing in beta-structure are broken upon complex formation with DNA and a new set of hydrogen bonds is formed between polypeptide amide groups and DNA base pairs. The code states a correspondence between four amino acid residues at a stereospecific site of the regulatory protein and an AT (GC) base pair at the control site. It predicts that there are six fundamental amino acid residues (serine, threonine, histidine, asparagine, glutamine and cysteine) whose arrangement in the stereospecific site determines the base pair sequence to which a given regulatory protein would bind preferentially.
Mol Biol Rep 1976 Apr
PMID:A code controlling specific binding of regulatory proteins to DNA. 127 65

The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.
Mol Cell Biochem 1992 Oct 07
PMID:Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation. 128 Mar 21

We have established the human nck sequence as a new oncogene. Nck encodes one SH2 and three SH3 domains, the Src homology motifs found in nonreceptor tyrosine kinases, Ras GTPase-activating protein, phosphatidylinositol 3-kinase, and phospholipase C-gamma. Overexpression of human nck in 3Y1 rat fibroblasts results in transformation as judged by alteration of cell morphology, colony formation in soft agar, and tumor formation in nude BALB/c mice. However, overexpression of nck does not induce detectable elevation of the phosphotyrosine content of specific proteins, as is observed for v-crk, another SH2/SH3-containing oncogene. Despite this fact, we demonstrate that Nck retains the ability to bind tyrosine phosphorylated proteins in vitro, using a fusion protein of Nck with glutathione-S-transferase (GST). Moreover, when incubated with lysates prepared from v-src-transformed 3Y1 cells or the nck-overexpressing cell lines, GST-Nck binds to both p60v-src and serine/threonine kinases, respectively. Although phosphotyrosine levels are not elevated in the nck-expressing fibroblasts, vanadate treatment of these cells results in a phosphotyrosine pattern that is altered from the parental 3Y1 pattern, suggestive of a perturbation of indigenous tyrosine kinase pathways. These results suggest the possibility that human nck induces transformation in 3Y1 fibroblasts by virtue of its altered affinity or specificity for the normal substrates of its rat homolog and that Nck may play a role in linking tyrosine and serine/threonine kinase pathways within the cell.
Mol Cell Biol 1992 Dec
PMID:The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels. 128 Mar 26

We previously reported a family with generalized resistance to thyroid hormone (GRTH) which had a point mutation with codon 448 CCT (proline) being converted to ACT (threonine) in the thyroid hormone receptor (TR) beta. To characterize functional properties of the mutant TR beta, transient expression studies were performed in COS cells. A double stranded oligonucleotide encompassing thyroid hormone response element (TRE) derived from the rat GH gene was synthesized. We constructed chloramphenicol acetyl transferase (CAT) plasmid containing the thymidine kinase promoter under the control of the rat GH TRE. T3 induction of CAT activity by the mutant TR beta was significantly reduced as compared with that of the normal TR beta. This was observed in the presence of 0.5-50 nM T3, but not at 500 nM T3. When the normal and mutant TR beta were cotransfected, the mutant TR beta inhibited gene activation regulated by the normal TR beta. However, a high molar excess was necessary to significantly inhibit the function of the normal receptor. Additionally, the binding of in vitro synthesized mutant TR beta to TRE was preserved.
Mol Cell Endocrinol 1992 Dec
PMID:Transcriptional activity of a mutant thyroid hormone receptor beta in a family with generalized resistance to thyroid hormone. 130 92

The Escherichia coli hns gene, which encodes the nucleoid protein H-NS, was deprived of its natural promoter and placed under the control of the inducible lambda PL promoter. An hns mutant yielding a protein (H-NS delta 12) with a deletion of four amino acids (Gly112-Arg-Thr-Pro115) was also obtained. Overproduction of wild-type (wt) H-NS, but not of H-NS delta 12, resulted in a drastic loss of cell viability. The molecular events and the morphological alterations eventually leading to cell death were investigated. A strong and nearly immediate inhibition of both RNA and protein synthesis were among the main effects of overproduction of wt H-NS, while synthesis of DNA and cell wall material was inhibited to a lesser extent and at a later time. Upon cryofixation of the cells, part of the overproduced protein was found in inclusion bodies, while the rest was localized by immunoelectron microscopy to the nucleoids. The nucleoids appeared condensed in cells expressing both forms of H-NS, but the morphological alterations were particularly dramatic in those overproducing wt H-NS; their nucleoids appeared very dense, compact and almost perfectly spherical. These results provide direct evidence for involvement of H-NS in control of the organization and compaction of the bacterial nucleoid in vivo and suggest that it may function, either directly or indirectly, as transcriptional repressor and translational inhibitor.
Mol Gen Genet 1992 Jan
PMID:Lethal overproduction of the Escherichia coli nucleoid protein H-NS: ultramicroscopic and molecular autopsy. 131 May 20

Previous studies in our laboratory showed nonrandom losses of chromosome 3p in association with tumorigenic transformation of SV40-immortalized human uroepithelial cells (HUC) to high grade cancers. To test the hypothesis that genes on 3p suppress HUC tumorigenesis, somatic cell hybrids were formed between nontumorigenic SV40-immortalized HUC and an isogeneic derivative transitional cell carcinoma line, MC-T16, that lost 3p on initial transformation. All hybrids were initially tumorigenically suppressed and reversion was always associated with genetic losses, including losses of 3p (Klingelhutz et al., Somatic Cell Mol. Genet., 17: 551-565, 1991). In this paper, we report that the smallest 3p region lost in a tumorigenic hybrid revertant (THR-X) in this system was an unusual interstitial deletion of 3p13----p21.2. Restriction fragment length polymorphism analysis confirmed this loss by showing that THR-X was reduced to homozygosity for D3S30, a 3p13 probe, but remained heterozygous for the distal 3p21.3 probe, D3F15S2. These data, along with our previous report identifying loss of 3p13----p14.2 as the smallest 3p region deleted in association with SV40-immortalized HUC tumorigenic transformation (Klingelhutz et al., Genes Chromosomes Cancer, 3: 346-357, 1991), provide compelling new evidence for a bladder cancer suppressor gene in the 3p13----p21.2 region.
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PMID:Loss of 3p13----p21.2 in tumorigenic reversion of a hybrid between isogeneic nontumorigenic and tumorigenic human uroepithelial cells. 131 37


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