Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have described in D. discoideum a highly organized cell aggregation that is mediated by cAMP. After suitable differentiation induced by starvation, the cells develop the capacity to orient in gradients of cAMP and to secrete cAMP in response to cAMP. This signaling response sets up the cell-cell relay of cAMP waves that transiently orients the cells toward the center. Both the signaling response and the chemotactic response, measured in isolated cells, adapt. The kinetics and properties of adaptation of the two responses are similar and may be due to the same mechanism. The mechanism does not involve protein synthesis, a change in the number or affinity of surface receptors, or the activation of adenylate cyclase. Adaptation of signaling is essential for the oscillatory production of cAMP at the aggregation centers and ensures that the cAMP waves move steadily toward the edge of the aggregation territories. Adaptation of the chemotactic response also ensures that cells do not reorient away from the center in the gradient presented by the trailing edge of the wave. We have demonstrated that both chemotaxis and cAMP signaling are mediated by the same surface receptor. The polypeptide containing the binding site of the receptor has been identified by photoaffinity labeling with [32P]-8-N3-cAMP as a diffuse band of 41,000-45,000 Mr. The receptor and adenylate cyclase copurify on a homogeneous class of vesicles resistant to extraction by nonionic detergents. A GTP-binding protein that is a substrate for cholera toxin-catalyzed ADP ribosylation is found in supernatants and membranes and may be similar to the Gs regulatory protein of adenylate cyclase in higher organisms. The mechanism of activation of the adenylate cyclase and chemotactic machinery is unknown. We have been able to inhibit the activation of the adenylate cyclase selectively and rapidly with agents acting to crosslink cell surface components, which may give a clue to the activation mechanism. The elaborate mechanisms of cell-cell communication occurring in D. discoideum are without precedent in biological literature, although models of oscillatory wave propagation have been proposed to account for pattern formation. Although it is unlikely that extracellular cAMP would be involved, it is not inconceivable that such mechanisms occur during the development of more evolutionarily advanced organisms. The organized communication system in D. discoideum is only apparent when cells are plated uniformly on a flat surface; such organized movements occurring in a three-dimensional structure such as an embryo would be very difficult to discern.
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PMID:Cell-cell interactions in the development of Dictyostelium. 285 27

Membrane integration of a nascent opsin polypeptide was examined to determine whether insertion of proteins into the endoplasmic reticulum is dependent upon energy provided by ribonucleotide triphosphate hydrolysis. A discrete-sized nascent chain was obtained by in vitro translation of a mRNA which lacked a termination codon yet encoded the first 156 residues of bovine opsin. Ribosomes bearing the newly synthesized opsin chains were post-translationally incubated with canine pancreas microsomal membrane vesicles after addition of exogenous ribonucleotides or ribonucleotide analogues. Post-translational membrane integration and glycosylation of the 156-residue nascent polypeptide was found to require either the presence of guanosine triphosphate or a nonhydrolyzable GTP analogue. ATP did not promote post-translational integration of the nascent polypeptide. Although ribonucleotide hydrolysis was not obligatorily required for integration of opsin, we observed an increase in the proportion of glycosylated opsin chains in post-translational incubations that contained hydrolyzable ribonucleotide triphosphates. We conclude that a GTP-binding protein performs an essential role during integration of opsin into the endoplasmic reticulum.
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PMID:Guanosine triphosphate promotes the post-translational integration of opsin into the endoplasmic reticulum membrane. 296 48

Chemosensory dendritic membranes (olfactory cilia) contain protein kinase activity that is stimulated by cyclic AMP and more efficiently by the nonhydrolyzable GTP analog guanosine-5'-O-(3-thio)triphosphate (GTP gamma S). In control nonsensory (respiratory) cilia, the cyclic AMP-dependent protein kinase is practically GTP gamma S-insensitive. GTP gamma S activation of the olfactory enzyme appears to be mediated by a stimulatory GTP-binding protein (G-protein) and adenylate cyclase previously shown to be enriched in the sensory membranes. Protein kinase C activity cannot be detected in the chemosensory cilia preparation under the conditions tested. Incubation of olfactory cilia with [gamma-32P]ATP leads to the incorporation of [32P]phosphate into many polypeptides, four of which undergo covalent modification in a cyclic nucleotide-dependent manner. The phosphorylation of one polypeptide, pp24, is strongly and specifically enhanced by cyclic AMP at concentrations lower than 1 microM. This phosphoprotein is not present in respiratory cilia, but is seen also in membranes prepared from olfactory neuroepithelium after cilia removal. Cyclic AMP-dependent protein kinase and phosphoprotein pp24 may be candidate components of the molecular machinery that transduces odor signals.
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PMID:Cyclic AMP-dependent protein phosphorylation in chemosensory neurons: identification of cyclic nucleotide-regulated phosphoproteins in olfactory cilia. 302 Jan 77

A GTP-binding protein serving as the specific substrate of islet-activating protein (IAP), pertussis toxin, was partially purified from Lubrol extract of sea urchin egg membranes. The partially purified protein possessed two polypeptides of 39 and 37 kDa; the 39 kDa polypeptide was specifically ADP-ribosylated by IAP and the 37 kDa protein cross-reacted with the antibody prepared against purified beta gamma-subunits of alpha beta gamma-heterotrimeric IAP substrates from rat brain. Incubation of this sea urchin IAP substrate with a non-hydrolyzable GTP analogue resulted in a reduction of the apparent molecular mass on a column of gel filtration as had been the case with purified rat brain IAP substrates, suggesting that the sea urchin IAP substrate was also a heterooligomer dissociable into two polypeptides in the presence of GTP analogues. Thus, the 39 and 37 kDa polypeptides of the sea urchin IAP substrate correspond to the alpha- and beta-subunits, respectively, of mammalian IAP substrates which are involved in the coupling between membrane receptor and effector systems.
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PMID:Guanine nucleotide-binding protein in sea urchin eggs serving as the specific substrate of islet-activating protein, pertussis toxin. 309 44

The requirement for ribonucleotides and ribonucleotide hydrolysis was examined at several distinct points during translocation of a secretory protein across the endoplasmic reticulum. We monitored binding of in vitro-assembled polysomes to microsomal membranes after removal of ATP and GTP. Ribonucleotides were not required for the initial low salt-insensitive attachment of the ribosome to the membrane. However, without ribonucleotides the nascent secretory chains were sensitive to protease digestion and were readily extracted from the membrane with either EDTA or 0.5 M KOAc. In contrast, nascent chains resisted extraction with either EDTA or 0.5 M KOAc and were insensitive to protease digestion after addition of GTP or nonhydrolyzable GTP analogues. Translocation of the nascent secretory polypeptide was detected only when ribosome binding was conducted in the presence of GTP. Thus, translocation-competent binding of the ribosome to the membrane requires the participation of a novel GTP-binding protein in addition to the signal recognition particle and the signal recognition particle receptor. The second event we examined was translocation and processing of a truncated secretory polypeptide. Membrane-bound polysomes bearing an 86-residue nascent chain were generated by translation of a truncated preprolactin mRNA. Ribonucleotide-independent translocation of the polypeptide was detected by cleavage of the 30-residue signal sequence after puromycin termination. Nascent chain transport, per se, is apparently dependent upon neither ribonucleotide hydrolysis nor continued elongation of the polypeptide once a functional ribosome-membrane junction has been established.
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PMID:Formation of a functional ribosome-membrane junction during translocation requires the participation of a GTP-binding protein. 309 28

The existence of a GTP-binding protein of the Ns type in Trypanosoma cruzi was explored. Epimastigote membranes were labelled by cholera toxin in the presence of [adenine-14C]NAD+. After SDS/polyacrylamide-gel electrophoresis of extracted membrane proteins, a single labelled polypeptide band of apparent Mr approx. 45,000 was detected. Epimastigote cells were treated with N-ethylmaleimide and electrofused to lymphoma S49 cells lacking the Ns protein. Evidence indicates that in such electrofusion-generated cell hybrids a heterologous adenylate cyclase system was reconstituted with the Ns protein provided by T. cruzi epimastigotes.
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PMID:Evidence for the existence of an Ns-type regulatory protein in Trypanosoma cruzi membranes. 309 61

The amino acid sequence of the alpha-subunit of Gi, the human adenylate cyclase inhibiting GTP-binding protein, has been deduced from the nucleotide sequence of a DNA clone complementary to Gi alpha mRNA from differentiated U937 cells. The cDNA encodes a polypeptide of 355 amino acids (Mr 40456). The amino acid sequence homology between human Gi alpha and rat, murine, and bovine Gi alpha is 98.6, 97.7 and 87.9% respectively. Differentiation of the U937 cells from monoblasts to monocyte-like cells resulted in a 3-fold increase in Gi alpha mRNA as well as a 3.6-fold increase in the 41 kDa pertussis toxin substrate presumed to be Gi alpha. Thus, increased levels of this G-protein are associated with monocyte differentiation and appear to be regulated transcriptionally.
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PMID:Human Gi protein alpha-subunit: deduction of amino acid structure from a cloned cDNA. 310 Mar 30

A GTP-binding protein serving as the specific substrate of islet-activating protein (IAP), pertussis toxin, was partially purified from human leukemic (HL-60) cells that had been differentiated into neutrophil type. The partially purified protein, referred to as GHL, predominantly consisted of at least two polypeptides with molecular masses of 40,000 daltons (alpha) and 36,000 or 35,000 daltons (beta). The structure was similar to Gi or Go previously purified from rat brain as an alpha beta gamma-heterotrimeric IAP substrate (Katada, T., Oinuma, M., and Ui, M. (1986) J. Biol. Chem. 261, 8182-8191), although the existence of the gamma of GHL was unclear. The 40,000-dalton polypeptide contained the site for IAP-catalyzed ADP-ribosylation and the binding site for guanine nucleotide with a high affinity. The 36,000- and 35,000-dalton polypeptides were cross-reacted with the affinity-purified antibody raised against the beta of brain Gi and Go. Limited proteolysis with trypsin and immunoblot analyses with the use of the affinity-purified antibodies raised against the alpha of brain Gi or Go indicated that the alpha of GHL was different from the alpha of Gi or Go. Kinetics of guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding to GHL was also quite different from that to brain Gi or Go. Incubation of GHL with GTP gamma S resulted in a resolution into GTP gamma S-bound alpha and beta(gamma) thus purified had abilities to inhibit a membrane-bound adenylate cyclase activity and to associate with the alpha of brain IAP substrate in a fashion similar to the beta gamma of brain IAP substrates, suggesting that there were no significant differences in the biological activities between the beta(gamma) of GHL and those of Gi or Go. Physiological roles of the new GTP-binding protein, GHL, purified from the neutrophil-like cells in receptor-mediated signal transduction are discussed.
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PMID:A new GTP-binding protein in differentiated human leukemic (HL-60) cells serving as the specific substrate of islet-activating protein, pertussis toxin. 311 Jan 46

A soluble inositolphospholipid-specific phospholipase C (PI-phospholipase C) has been purified 5,800-fold from the cytosolic fraction of calf thymocytes. The purification was achieved by sequential column chromatographies on DEAE-Sepharose CL-6B, heparin-Sepharose CL-6B, Sephacryl S-300, Mono S, and Superose 12, followed by column chromatography on Sephadex G-100 in the presence of 1% sodium cholate. The enzyme thus purified was found to be homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight of the enzyme was estimated to be 68 kDa by SDS-PAGE. The enzyme is specific for inositol phospholipids. Phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate (PIP2) were hydrolyzed, but phosphatidylcholine and phosphatidylethanolamine were not affected by the enzyme. GTP gamma S-binding activity was detected in the enzyme fractions after all the purification steps, but not in the final enzyme preparation. The PI-phospholipase C and GTP gamma S-binding activities in the partially purified enzyme preparation could be separated by the column chromatography on Sephadex G-100 only in the presence of 1% sodium cholate. Thus, the soluble PI-phospholipase C has affinity to a GTP-binding protein. SDS-PAGE of the GTP-binding fractions eluted from the Sephadex G-100 column gave three visible bands of 54, 41, and 27 kDa polypeptide was specifically ADP-ribosylated by pertussis toxin. Furthermore, it was found that GTP and GTP gamma S (10 microM and 1 mM) could enhance the PIP2 hydrolysis activity of the partially purified enzyme in the presence of 3 mM EGTA, but the purified enzyme after separation from the GTP-binding activity was not affected by GTP and GTP gamma S. The soluble PI-phospholipase C of calf thymocytes may be not only physically but also functionally associated with a GTP-binding protein.
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PMID:Physical and functional association of cytosolic inositolphospholipid-specific phospholipase C of calf thymocytes with a GTP-binding protein. 312 64

Application of a differential hybridization technique led to the isolation of a human pituitary cDNA clone encoding the complete structure of the polypeptide 7B2. This protein of unknown function, which is sorted to secretory granules, appears to be present selectively in neurons and endocrine cells. The polypeptide chain of human 7B2, preceded by a cleaved signal peptide, comprises 185 amino acids (a calculated Mr of 20,793). Interesting features of the highly-conserved 7B2 structure include (i) a serine phosphorylation consensus sequence, (ii) the occurrence of three pairs of dibasic amino acids representing potential proteolytic cleavage sites and, in particular, (iii) the presence of three regions homologous to GTP-binding domains giving 7B2 structural characteristics of a GTP-binding protein.
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PMID:Cloning and sequence analysis of human pituitary cDNA encoding the novel polypeptide 7B2. 313 53


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