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

Expression of the yeast Saccharomyces cerevisiae SRP1 (Serine-rich Protein) gene is shown here to be induced both by low temperature and anaerobic growth conditions. We show that anaerobic SRP1 expression is haem-dependent; however, haem influence does not operate through the action of the hypoxic-gene ROX1 repressor. The SRP1 promoter region displaying the stress-responsive elements is restricted to its first 551 bp, upstream of the initiation codon, although an upstream activation site contained in upstream sequences is required for full promoter activity. In addition, we demonstrate that the TIP1 gene, sharing similar nucleotide and polypeptide structure with SRP1, and previously reported to be a cold-shock-inducible gene, is also a hypoxic gene. Srp1 protein production is similarly induced by low temperature and anaerobic growth conditions. This protein, detected in the plasma membrane fraction, is shown to be exposed on the cell surface via a glycosyl-phosphatidylinositol membrane anchoring.
Mol Microbiol 1996 Apr
PMID:Regulation by low temperatures and anaerobiosis of a yeast gene specifying a putative GPI-anchored plasma membrane protein [corrected]. 873 42

Gal4p regulates expression of genes necessary for galactose catabolism in Saccharomyces cerevisiae. We have previously shown that phosphorylation of Gal4p requires both its DNA binding and transcriptional-activation functions and have suggested that phosphorylation occurs as a consequence of interaction with general transcription factors. In this study, we show that phosphorylation occurs rapidly on a limited fraction of overexpressed Gal4p present in a sodium dodecyl sulfate-extractable subcellular fraction while a significant fraction remains stably unphosphorylated. Taken together with our previous observations, we conclude that Gal4p is phosphorylated only if it becomes localized to the nucleus and is capable of both DNA binding and transcriptional activation. We demonstrate that Gal4p is multiply phosphorylated at both the C and N termini, and we identify the precise locations of three sites of phosphorylation at serines 691, 696, and 699. Of these sites, only serine 699 must be phosphorylated for galactose-inducible transcription to occur. Mutation of S-699 to alanine significantly impairs GAL induction by galactose in GAL80+ cells but does not affect transcriptional activation by Gal4p in gal80- cells. In gal80- cells, Gal4p phosphorylation, including that of serine 699, is stimulated by the presence of both galactose and glucose, indicating that phosphorylation at this site is not specifically activated by galactose. Serine 699 phosphorylation requires Gal4p's DNA binding function and is influenced by the function of the RNA polymerase II holoenzyme component Gal11p. These results suggest that a phosphorylation on Gal4p, likely resulting from interaction with the holoenzyme, modulates the induction process by regulating interaction between Gal4p and Gal80p.
Mol Cell Biol 1996 Sep
PMID:Phosphorylation of Ga14p at a single C-terminal residue is necessary for galactose-inducible transcription. 875 47

Serine acetyltransferase, a key enzyme in the L-cysteine biosynthetic pathway of sulfate assimilating organisms, catalyzes the formation of O-acetylserine, the immediate precursor of L-cysteine. In higher plants, it is thought that sulfur assimilation occurs primarily in leaf chloroplasts; however, serine acetyltransferase is not localized exclusively in this tissue and organelle. At least three genes for serine acetyltransferase have been identified in the higher plant Arabidopsis thaliana. Reported here is a cDNA corresponding to one of these genes, SAT1, a 1,079 bp clone with an open reading frame predicted to encode a 34-kDa protein that is able to functionally complement a serine acetyltransferase mutant strain of Escherichia coli. The predicted amino acid sequence of SAT1 shows significant homology with bacterial serine acetyltransferases. SAT1, expressed as a recombinant protein, shows serine acetyltransferase enzyme activity and cross-reacts with an antibody against the homologous E. coli enzyme. The first 40 amino acids of the SAT1 polypeptide resembles a plastid transit peptide, but the polypeptide is probably not plastid localized. Genomic DNA blot analysis of A. thaliana showed that SAT1 is a single copy gene and RNA blot analysis revealed that SAT1 is expressed in both leaves and roots.
Cell Mol Biol Res 1995
PMID:Serine acetyltransferase from Arabidopsis thaliana can functionally complement the cysteine requirement of a cysE mutant strain of Escherichia coli. 886 90

Mouse glucocorticoid receptors (GRs) are phosphorylated in the N-terminal domain at serine/ threonine residues, most lying in consensus sequences for cell cycle-associated kinases. Glucocorticoid agonists, but not antagonists, induce hyperphosphorylation. Phosphorylation of GRs overexpressed in Chinese hamster ovary (CHO) cells is cell cycle-dependent: basal phosphorylation in S phase is one third that in G2/M; glucocorticoids induce hyperphosphorylation in S but not G2/M, paralleling the reported sensitivity in S and resistance in G2/M of proliferating cells to transcriptional activation by glucocorticoids. This parallel led us to investigate what controls hyperphosphorylation. We tested three hypotheses: hyperphosphorylation is controlled by 1) negative charge due to basal GR phosphorylation, being permitted in S by low charge and blocked in G2/M by high charge; 2) presence in S and absence in G2/M of required kinases; 3) availability in S and lack in G2/M of unoccupied phosphorylatable sites. Our results are inconsistent with 2) and 3), but strongly support 1). GR mutants with alanines (A7GR) or glutamates (E7GR) replacing all but one phosphorylated site were overexpressed in CHO cells. Serine 122 remained intact to report GR phosphorylation. Consistent with hypothesis 1, with A7GRs hormone-induced hyperphosphorylation occurred in both S and G2/M (thus revealing kinase activity for hyperphosphorylation of at least serine 122 in both phases), whereas with E7GRs it occurred in neither phase. We conclude that basal GR phosphorylation controls hormone-induced GR hyperphosphorylation by modulating negative charge in the N-terminal domain and could potentially control other cell cycle-dependent GR properties.
Mol Endocrinol 1997 Mar
PMID:Control by basal phosphorylation of cell cycle-dependent, hormone-induced glucocorticoid receptor hyperphosphorylation. 905 77

We investigated several indices involved in sphingomyelin metabolism in developing rat lung. The levels of sphingomyelin gradually increased during lung maturation, with highest levels observed postnatally. The content of sphingosine and ceramide, biologically active sphingomyelin degradation products, did not significantly change in microsomes during the prenatal period, but increased to peak levels in neonatal and adult lung, respectively. Sphingosine content increased 6-fold between the fetal (Day 21) and neonatal period. The developmental profiles of two enzymes involved in sphingomyelin synthesis, serine palmitoyltransferase and sphingomyelin synthase, were similar. Serine palmitoyltransferase activity increased progressively from the fetal to neonatal period, and plateaued at high levels in the adult lung. The activity of serine palmitoyltransferase correlated with the levels of endogenous sphingolipid in lung tissue. Sphingomyelin synthase activity also increased during fetal lung development, but attained highest levels at Day 21 gestation; postnatally, enzyme activity was detected at lower levels. The activities of the sphingolipid hydrolases, acid and neutral sphingomyelinase and acid and alkaline ceramidase, were elevated in fetal lung, thereafter declining to low levels after birth. Studies conducted in alveolar macrophages, fibroblasts, and alveolar type II epithelial cells revealed that these developmental changes in enzyme activities in lung tissue were also occuring globally at the cellular level and were not restricted to any specific cell population. These studies suggest that the developmental increase in lung sphingomyelin content is due to coordinate regulation of enzymes involved in the biosynthesis and degradation of sphingomyelin. These observations also suggest a regulatory role for serine palmitoyltransferase in the generation of long chain sphingoid bases.
Am J Respir Cell Mol Biol 1997 May
PMID:Sphingomyelin metabolism is developmentally regulated in rat lung. 916 Aug 43

Tissue plasminogen activator (tPA), the serine protease that converts inactive plasminogen to the protease plasmin, was recently shown to mediate neurodegeneration in the mouse hippocampus. Mice deficient in tissue plasminogen activator (tPA) display a dramatic resistance to a paradigm of excitotoxic neuronal death that involves intrahippocampal injection of the excitotoxin. This model is thought to reproduce the mechanism of neuronal death observed during acute (such as ischemic stroke) and degenerative (such as amyotrophic lateral sclerosis) diseases of the nervous system. The requirement for the proteolytic activity of tPA to mediate neuronal death is acute in the adult mouse. Serine protease inhibitors, specific for tPA or the tPA/plasmin proteolytic cascade, are effective in conferring extensive neuroprotection following the excitotoxic injection. These findings suggest possible new ways for interfering with the neuronal death observed in the hippocampus as a result of excitotoxicity. In addition, tPA is produced in the hippocampus primarily by microglial cells, which become activated in response to the neuronal injury. Blocking microglial activation has been shown in other injury paradigms to protect against neuronal death, therefore suggesting another way to retard neurodegeneration in the CNS. Furthermore, after the insult has been inflicted and in the presence of a compromised blood-brain barrier macrophages (cells deriving from the same lineage as microglia) migrate into the brain, where they are thought to contribute to the neuronal cell loss by secreting neurotoxic molecules. If these macrophages/microglia expressed, however, a tPA inhibitor, rather than the possibly neurotoxic tPA, they might be able to protect the neurons from dying.
J Mol Med (Berl) 1997 May
PMID:Clinical implications of the involvement of tPA in neuronal cell death. 918 75

The retinoblastoma protein (pRb) inhibits progression through the cell cycle. Although pRb is phosphorylated when G1 cyclin-dependent kinases (Cdks) are active, the mechanisms underlying pRb regulation are unknown. In vitro phosphorylation by cyclin D1/Cdk4 leads to inactivation of pRb in a microinjection-based in vivo cell cycle assay. In contrast, phosphorylation of pRb by Cdk2 or Cdk3 in complexes with A- or E-type cyclins is not sufficient to inactivate pRb function in this assay, despite extensive phosphorylation and conversion to a slowly migrating "hyperphosphorylated form." The differential effects of phosphorylation on pRb function coincide with modification of distinct sets of sites. Serine 795 is phosphorylated efficiently by Cdk4, even in the absence of an intact LXCXE motif in cyclin D, but not by Cdk2 or Cdk3. Mutation of serine 795 to alanine prevents pRb inactivation by Cdk4 phosphorylation in the microinjection assay. This study identifies a residue whose phosphorylation is critical for inactivation of pRb-mediated growth suppression, and it indicates that hyperphosphorylation and inactivation of pRb are not necessarily synonymous.
Mol Biol Cell 1997 Feb
PMID:Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. 919 Feb 8

Serine-arginine (SR)-rich proteins are believed to be important in mediating alternative pre-mRNA splicing. HRS/SRp40 expression is elevated in liver cell proliferation during development, regeneration, and oncogenesis. We tested whether HRS expression correlates with the appearance of alternatively spliced fibronectin transcripts during liver growth. HRS was highly expressed during the proliferative phase of liver development, correlating with expression of the fibronectin EIIIB alternative exon. In regenerating liver, HRS protein was induced in a time course consistent with the observed increase in fibronectin transcripts containing the EIIIB exon, particularly in nonparenchymal liver cells. Furthermore, in an in vivo assay, HRS, and not other SR proteins, directly mediated EIIIB exon inclusion in the fibronectin transcript. This alternative splicing was dependent on a purine-rich region within the EIIIB exon to which HRS specifically bound. We have established that HRS has the potential to contribute to the regulation of fibronectin pre-mRNA splicing during liver growth. Changes in fibronectin forms may be important in modifying liver architecture during the proliferative response, thus providing a potential mechanism by which SR proteins may participate in cellular growth control.
Mol Cell Biol 1997 Jul
PMID:HRS/SRp40-mediated inclusion of the fibronectin EIIIB exon, a possible cause of increased EIIIB expression in proliferating liver. 919 45

Serine/arginine (SR)-rich splicing factors contain an RNA binding domain and an arginine/serine (RS)-rich domain required for protein-protein interactions. In addition to their roles in the basic splicing reaction, SR proteins function as components of splicing enhancer complexes. Here, we investigate the role of RS domains in splicing enhancer function. Hybrid proteins containing RS domains fused to the MS2 RNA binding protein were tested in vitro with RNA substrates bearing an MS2 recognition sequence. These hybrid proteins activated splicing in nuclear extracts, but not in S100 extracts lacking SR proteins. However, intact recombinant SR proteins could complement the activity of the hybrid proteins in S100 extracts. These data demonstrate that RS domains function as splicing activators and suggest that the general and enhancer-dependent functions of SR proteins can be uncoupled.
Mol Cell 1998 Apr
PMID:Arginine/serine-rich domains of SR proteins can function as activators of pre-mRNA splicing. 966 Sep 60

We previously showed that a variety of amino acid substitutions at positions 58 and 59 in the V(H) CDR2 of an anti-arsonate (Ars) antibody Fab simultaneously resulted in increased or unaltered affinity for Ars and substantially enhanced affinity for DNA. To test the generality of these observations, we generated and characterized several antibody phage display libraries of this Fab containing random amino acid substitutions at V(H) CDR2 position 55. Position 55 was randomized in two contexts; in the unmutated V region, and in a previously isolated V(H) CDR2 position 58 and 59 mutant that displayed binding to both Ars and ssDNA. In the unmutated V region context, mutants that displayed strong binding to both Ars and DNA nearly exclusively contained Arginine residues at position 55. In the context of the 58 and 59 mutations, a variety of amino acid residues were observed at position 55 among mutants that bound strongly to both Ars and DNA, including Arginine, Lysine and Serine. None of these position 55 mutations measurable altered affinity for Ars. These data substantiate the view that "dual reactive" antibodies--specific for both a foreign and an autoantigen--are frequently generated in vivo via hypermutation during immune responses driven by the foreign antigen.
Mol Immunol 1997 Dec
PMID:Single amino acid substitutions in V(H) CDR2 are sufficient to generate or enhance the specificity of two forms of an anti-arsonate antibody variable region for DNA. 968 70


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