Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) stimulation of human neutrophils leads to a rapid increase of the cytosolic free Ca2+ concentration, [Ca2+]i, which is significantly reduced by removal of extracellular calcium. In the present study we show that fMet-Leu-Phe-induced [Ca2+]i increases are, in part, mediated by an increase of the plasma membrane permeability to Ca2+. This conclusion is based on the following evidence. In the presence of extracellular calcium, addition of La3+ reduced the fMet-Leu-Phe-induced [Ca2+]i increase to approximately the same level as that observed in the absence of extracellular calcium. A net increase of the plasma membrane permeability for Mn2+ could be observed after fMet-Leu-Phe stimulation, as revealed by intracellular quenching of the quin2 signal. The influx of Mn2+, like that of Ca2+, was inhibited by La3+ and was more pronounced in the absence of extracellular Ca2+, suggesting competition for the same pathway. Temporal dissociation of intracellular Ca2+ release from stores and Ca2+ influx from the medium could be demonstrated by readdition of calcium to cells stimulated in the absence of this cation. This second [Ca2+]i increase could be abolished either by giving the specific chemotactic peptide receptor antagonist, BOC-Met-Leu-Phe, or Co2+. We could also show that the fMet-Leu-Phe-dependent Ca2+ influx was not due to the activation of voltage-dependent calcium channels since depolarization either by K+ or gramicidin D did not affect the resting [Ca2+]i, nor did it affect a subsequent [Ca2+]i increase induced by fMet-Leu-Phe. Furthermore, nifedipine and verapamil, at concentrations known to block classical voltage-dependent calcium channels, had no significant effects on the Ca2+ influx induced by fMet-Leu-Phe. We suggest that fMet-Leu-Phe promotes influx of Ca2+ ions across the plasma membrane of human neutrophils by opening of receptor-dependent calcium channels.
Mol Pharmacol 1986 Nov
PMID:Characterization of fMet-Leu-Phe receptor-mediated Ca2+ influx across the plasma membrane of human neutrophils. 243 Jan 68

Microinjection of monoclonal antibody Y13-259, which reacts with all known mammalian and yeast ras-encoded proteins, has previously been shown to prevent NIH 3T3 cells from entering the S phase (L. S. Mulcahy, M. R. Smith, and D. W. Stacey, Nature [London] 313:241-243, 1985). We have now found several transformation-competent mutant v-rasH genes whose protein products in transformed NIH 3T3 cells are not immunoprecipitated by this monoclonal antibody. These mutant proteins are, however, precipitated by a different anti-ras antibody. Each of these mutants lacks Met-72 of v-rasH. In contrast to the result for cells transformed by wild-type v-rasH, Y13-259 microinjection of NIH 3T3 cells transformed by these mutant ras genes did not prevent the cells from entering the S phase. These results imply that a transformation-competent ras gene can supply a normal essential function for NIH 3T3 cells. When the proteins encoded by the mutant ras genes were overproduced in Escherichia coli, several mutant proteins that lacked Met-72 failed to bind Y13-259 in a Western blot. However, a ras protein from a mutant lacking amino antibody, but a ras protein from a mutant lacking amino acids 72 to 84 did not. These results suggest that Y13-259 may bind to a higher ordered structure that has been restored in the mutant lacking amino acids 72 to 82.
Mol Cell Biol 1986 May
PMID:A transforming ras gene can provide an essential function ordinarily supplied by an endogenous ras gene. 243 Dec 87

We have examined transcriptional start sites responsible for expression of the transposase and transposition inhibitor proteins encoded by IS50R, and determined the likely translational start site of transposase. Amino-terminal analysis of a transposase-beta-galactosidase fusion protein gave the sequence Met-Ile-Thr-Ser-Ala, which corresponds to the predicted amino acid sequence starting at position 93 of IS50. S1 nuclease mapping of IS50 RNA produced in vivo indicated that three transcripts, T1, T2 and T3, start near this position. Only T1 starts upstream from the transposase amino terminus. T2 corresponds to an in-vitro transcript described previously. Analysis of the transcripts and proteins produced from deletion derivatives of an IS50-lacZ construct suggested that the three transcripts initiate at independent but overlapping promoters clustered near the end of IS50. This analysis confirmed that only T1 can encode transposase, and that T2 is largely responsible for expression of the inhibitor protein. The coding capacity of T3 was not determined. Finally, transcripts that originate outside of IS50 are prevented from expressing transposase because of a secondary structure that is present in these transcripts only.
J Mol Biol 1986 Dec 20
PMID:Transcriptional and translational initiation sites of IS50. Control of transposase and inhibitor expression. 243 19

We assume that each class of protein has a core structure that is defined by internal residues, and that the external, solvent-contacting residues contribute to the stability of the structure, are of primary importance to function, but do not determine the architecture of the core portions of the polypeptide chain. An algorithm has been developed to supply a list of permitted sequences of internal residues compatible with a known core structure. This list is referred to as the tertiary template for that structure. In general the positions in the template are not sequentially adjacent and are distributed throughout the polypeptide chain. The template is derived using the fixed positions for the main-chain and beta-carbon atoms in the test structure and selected stereochemical rules. The focus of this paper is on the use of two packing criteria: avoidance of steric overlap and complete filling of available space. The program also notes potential polar group interactions and disulfide bonds as well as possible burial of formal charges. Central to the algorithm is the side-chain rotamer library. In an update of earlier studies by others, we show that 17 of the 20 amino acids (omitting Met, Lys and Arg) can be represented adequately by 67 side-chain rotamers. A list of chi angles and their standard deviations is given. The newer, high-resolution, refined structures in the Brookhaven Protein Data Bank show similar mean chi values, but have much smaller deviations than those of earlier studies. This suggests that a rotamer library may be a better structural approximation than was previously thought. In using packing constraints, it has been found essential to include all hydrogen atoms specifically. The "unified atom" representation is not adequate. The permitted rotamer sequences are severely restricted by the main-chain plus beta-carbon atoms of the test structure. Further restriction is introduced if the full set of atoms of the external residues are held fixed, the full-chain model. The space-filling requirement has a major role in restricting the template lists. The preliminary tests reported here make it appear likely that templates prepared from the currently known core structures will be able to discriminate between these structures. The templates should thus be useful in deciding whether a sequence of unknown tertiary structure fits any of the known core classes and, if a fit is found, how the sequence should be aligned in three dimensions to fit the core of that class.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1987 Feb 20
PMID:Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. 244 Oct 69

We have studied the contractile response and phosphoinositide hydrolysis induced by substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and Alp-Phe-Phe(R)-Gly[ANC-2]-Leu-Met-NH2 (L 363851), a selective NK2-receptor agonist, in guinea pig tracheal smooth muscle. The four tachykinins elicited a concentration-dependent contraction in tracheal smooth muscle devoid of epithelium, with the following order of potency: NKA greater than L 363851 greater than NKB greater than SP, (EC50 1.0 x 10(-9) M, 3.2 x 10(-9) M, 7.5 x 10(-9) M and 1.2 x 10(-7) M, respectively), which suggests that NK2 receptors predominate in airway smooth muscle. In the presence of epithelium, the sensitivity of airway smooth muscle to tachykinins was decreased, and the concentration response curves to tachykinins were shifted rightward by 30-fold for SP, 9-fold for NKA, and 5-fold for NKB. The concentration response curve to L 363851 was not significantly shifted in the presence of epithelium. This suggests that epithelium may release a relaxant factor in response to tachykinins via an NK1 receptor. In airway smooth muscle, we found that tachykinins elicited phosphoinositide breakdown with an order of potency similar to that for contractile response (EC50 2.2 x 10(-5) M, 3.6 x 10(-5) M, 4.4 x 10(-5) M, and 5.9 x 10(-5) M). In epithelium, SP alone elicited a significant phosphoinositide breakdown, suggesting that epithelial receptors to tachykinins may be of the NK1 subtype. Since it is established that phosphoinositide derivatives can elicit mobilization of intracellular calcium, our results suggest that phosphoinositide breakdown is the coupling mechanism for tachykinin-induced contraction of airway smooth muscle.
Mol Pharmacol 1988 May
PMID:Tachykinin-induced phosphoinositide breakdown in airway smooth muscle and epithelium: relationship to contraction. 245 69

A clone encoding a recombinant protein which reacted strongly with human antibodies from a donor clinically immune to malaria, was isolated from a genomic Plasmodium falciparum library. Mice injected with this protein, designated 10b, produced antibodies which reacted with all developmental stages of erythrocytic asexual parasites in indirect immunofluorescence. In immunoblotting, the same antibodies recognized two P. falciparum polypeptides of 36 kDa and 33 kDa. Of three monoclonal antibodies raised against the 10b recombinant protein, two inhibited parasite reinvasion of erythrocytes in an isolate specific manner. Surprisingly, however, the third was found to significantly enhance reinvasion of erythrocytes and also to induce a more rapid maturation of intraerythrocytic parasites in all isolates tested. Nucleotide sequence analysis of the 1124 bp insert revealed that it encodes a protein which consists of 30% asparagine and contains three asparagine rich, imperfect tandem repeats: Lys-Lys-Asn-Asn (3x), Met-Asn-His/Gln-Pro-Asn-Asn (14x), and Lys-Asn-Asn-Asn-Asn (7x).
Mol Biochem Parasitol 1989 Jan 15
PMID:Enhancement or inhibition of Plasmodium falciparum erythrocyte reinvasion in vitro by antibodies to an asparagine rich protein. 246 5

The nucleotide sequences of the complete set of tRNA species in Mycoplasma capricolum, a derivative of Gram-positive eubacteria, have been determined. This bacterium represents the first genetic system in which the sequences of all the tRNA species have been determined at the RNA level. There are 29 tRNA species: three for Leu, two each for Arg, Ile, Lys, Met, Ser, Thr and Trp, and one each for the other 12 amino acids as judged from aminoacylation and the anticodon nucleotide sequences. The number of tRNA species is the smallest among all known genetic systems except for mitochondria. The tRNA anticodon sequences have revealed several features characteristic of M. capricolum. (1) There is only one tRNA species each for Ala, Gly, Leu, Pro, Ser and Val family boxes (4-codon boxes), and these tRNAs all have an unmodified U residue at the first position of the anticodon. (2) There are two tRNAThr species having anticodons UGU and AGU; the first positions of these anticodons are unmodified. (3) There is only one tRNA with anticodon ICG in the Arg family box (CGN); this tRNA can translate codons CGU, CGC and CGA. No tRNA capable of translating codon CGG has been detected, suggesting that CGG is an unassigned codon in this bacterium. (4) A tRNATrp with anticodon UCA is present, and reads codon UGA as Trp. On the basis of these and other observations, novel codon recognition patterns in M. capricolum are proposed. A comparatively small total, 13, of modified nucleosides is contained in all M. capricolum tRNAs. The 5' end nucleoside of the T psi C-loop (position 54) of all tRNAs is uridine, not modified to ribothymidine. The anticodon composition, and hence codon recognition patterns, of M. capricolum tRNAs resemble those of mitochondrial tRNAs.
J Mol Biol 1989 Sep 05
PMID:Codon recognition patterns as deduced from sequences of the complete set of transfer RNA species in Mycoplasma capricolum. Resemblance to mitochondria. 247 13

Reversed-phase chromatography (RPC) was used to resolve two variants of recombinant amino terminal methionyl residue (N-Met) insulin-like growth factor-I (IGF-I) with the same amino acid constitution but different disulphide linkages. Following radioiodination, equilibration with plasma and size exclusion chromatography at neutral pH the major form on RPC (approximate abundance 60%) demonstrated greater than 80% binding to 150 kDa and 40-50 kDa IGF binding proteins. This peptide has the RPC elution characteristics and disulphide assignment (Cys6-Cys48, Cys18-Cys61, Cys47-Cys52) of authentic with mismatched disulphides (Cys6-Cys47, Cys18-Cys61, Cys48-Cys52; N-Met IGF-I peak 1 peptide) demonstrated less than 15% binding under similar conditions. Potency of the peptides was investigated in competitive IGF-I plasma binding protein and L6 myoblast radioreceptor assays. The peak 2 peptide proved equipotent to purified ovine plasma IGF-I in each system but by contrast the peak 1 peptide was 40-fold and 200-fold less potent in the binding protein and radioreceptor assays respectively. Biological potency was examined in a non-competitive assay based on incorporation of [3H]leucine into confluent cultures of L6 myoblasts. In this system the N-Met IGF-I peak 1 peptide proved 15-fold less potent than the peak 2 peptide with correct disulphide linkages. Refolding variants may prove useful in establishing structure/function relationships for IGF-I.
Mol Cell Endocrinol 1989 Sep
PMID:Binding protein, radioreceptor and biological activities of recombinant methionyl insulin-like growth factor-I variants. 247 83

The reassignment of codon AUA from isoleucine to methionine during mitochondrial evolution may be explained by the codon reassignment (capture) hypothesis without assuming direct replacement of isoleucine by methionine in mitochondrial proteins. According to this hypothesis, codon AUA would have disappeared from the reading frames of messenger RNA. AUA codons would have mutated mainly to AUU isoleucine codons because of constraints resulting from elimination of tRNA Ile with anticodon *CAU (in which *C is lysidine). Later, tRNA Met (CAU) would have undergone structural changes enabling it to pair with both AUG and AUA. AUA codons, formed by mutations of other codons, including AUG, would have reappeared and would have been translated as methionine.
J Mol Evol 1989 Nov
PMID:Evolution of the mitochondrial genetic code. II. Reassignment of codon AUA from isoleucine to methionine. 251 89

The structural organization of the low molecular mass form (43 kDa) of Bordetella pertussis adenylate cyclase was dissected taking advantage of the known sequence of the bacterial cya gene (Glaser, P., Ladant, D., Sezer, O., Pichot, F., Ullmann, A., and Danchin, A. (1988) Mol. Microbiol. 2, 19-30) and its low content of Trp and Met residues. Cleavage of the 43-kDa protein and of its complementary tryptic fragments (T25 and T18 peptides) with N-chlorosuccinimide and cyanogen bromide followed by sodium dodecyl sulfate-polyacrylamide gel analysis of digestion products allowed the following conclusions: (i) the catalytically active 43-kDa form of B. pertussis adenylate cyclase is within the first 400 residues of the protein encoded by the cya gene. T25 occupies the N-terminal domain of the protein (residues 1-235/237). Isolated T25 fragment exhibits a low but measurable enzymatic activity which indicates that it harbors the catalytic site; (ii) T18 which is the main calmodulin-binding domain, occupies the C-terminal segment of protein (residues 236/238-399) and is devoid of catalytic properties; (iii) the two complementary peptides T25 and T18 reassociated only in the presence of calmodulin, leading to significant recovery of the original activity. These results demonstrate that both fragments of the 43-kDa form of adenylate cyclase are essential for a high level of enzymatic activity.
 ...
PMID:Characterization of the calmodulin-binding and of the catalytic domains of Bordetella pertussis adenylate cyclase. 253 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>