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

Screening of a human embryonic lung fibroblast cDNA expression library with antiphosphotyrosine antibodies led to isolation of a novel protein kinase. A clone, designated A6, contained a 3-kb cDNA insert with a predicted open reading frame of 350 amino acids. DNA sequence analysis failed to reveal any detectable similarity with previously known genes, and the predicted A6 protein lacked any of the motifs commonly conserved in the catalytic domains of protein kinases. However, the bacterially expressed beta-galactosidase-A6 fusion protein demonstrated both tyrosine and serine phosphorylation in an in vitro kinase assay and phosphorylated exogenous substrates including myelin basic protein specifically on tyrosine residues. The enzyme also displayed biochemical properties analogous to those of other protein tyrosine kinases. The A6 gene was found to be expressed widely at the transcript level in normal tissues and was evolutionarily conserved. Thus, A6 represents a novel tyrosine kinase which is highly divergent from previously described members of this important class of regulatory molecules.
Mol Cell Biol 1994 Feb
PMID:Prokaryotic expression cloning of a novel human tyrosine kinase. 750 8

The conservation in evolution of fundamental signal transduction modules offers a means of isolating genes likely to be involved in plant development. We have amplified by PCR Arabidopsis cDNA and genomic sequences related to the product of the shaggy/zeste-white 3 (sgg) segment polarity gene of Drosophila. This regulatory protein is functionally homologous to glycogen synthase kinase-3 in mammals (GSK-3), which regulates, among others, the DNA-binding activity of the c-jun/AP1 transcription factor. Analysis of PCR products led to the identification of five genes; for two of which, corresponding full-length cDNAs, ASK-alpha and gamma (for Arabidopsis shaggy-related protein kinase), were characterized. The encoded proteins were 70% identical to GSK-3 and sgg over the protein kinase catalytic domain and, after production in Escherichia coli, autophosphorylated mainly on threonine and serine residues, but phosphotyrosine was also detected. ASK-alpha and ASK-gamma also phosphorylated phosphatase inhibitor-2 and myelin basic protein, on threonine and serine, respectively. The high conservation of the protein kinases of GSK-3 family, and their action at the transcriptional level, suggest that the ASK proteins have important functions in higher plants.
Mol Gen Genet 1994 Feb
PMID:Arabidopsis homologs of the shaggy and GSK-3 protein kinases: molecular cloning and functional expression in Escherichia coli. 750 23

A novel protein, p55CDC, has been identified in cycling mammalian cells. This transcript is readily detectable in all exponentially growing cell lines but disappears when cells are chemically induced to fall out of the cell cycle and differentiate. The p55CDC protein appears to be essential for cell division, since transfection of antisense p55CDC cDNA into CHO cells resulted in isolation of only those cells which exhibited a compensatory increase in p55CDC transcripts in the sense orientation. Immunoprecipitation of p55CDC yielded protein complexes with kinase activity which fluctuated during the cell cycle. Since p55CDC does not have the conserved protein kinase domains, this activity must be due to one or more of the associated proteins in the immune complex. The highest levels of protein kinase activity were seen with alpha-casein and myelin basic protein as substrates and demonstrated a pattern of activity distinct from that described for the known cyclin-dependent cell division kinases. The p55CDC protein was also phosphorylated in dividing cells. The amino acid sequence of p55CDC contains seven repeats homologous to the beta subunit of G proteins, and the highest degree of homology in these repeats was found with the Saccharomyces cerevisiae Cdc20 and Cdc4 proteins, which have been proposed to be involved in the formation of a functional bipolar mitotic spindle in yeast cells. The G beta repeat has been postulated to mediate protein-protein interactions and, in p55CDC, may modulate its association with a unique cell cycle protein kinase. These findings suggest that p55CDC is a component of the mammalian cell cycle mechanism.
Mol Cell Biol 1994 May
PMID:A novel mammalian protein, p55CDC, present in dividing cells is associated with protein kinase activity and has homology to the Saccharomyces cerevisiae cell division cycle proteins Cdc20 and Cdc4. 751 50

The Golli-mbp gene complex contains two overlapping transcription units with two distinct promoters, of which the downstream (myelin basic protein [mbp]) promoter is more frequently used. A previous comparison of the downstream promoter sequences from shark and mouse allowed the identification of two DNA sequences called the boxes I and II and the wobble zone. The boxes I and II sequence is a composite cis-acting motif that is thought to be involved in the regulation of the downstream promoter. It contains sequences similar to T-antigen, MyoD/E2A, and glucocorticoid receptor-binding sites. The wobble zone codes for an exon (5a in the nomenclature of Campagnoni et al., 1993) that is included in messenger RNAs transcribed from the upstream promoter. The polypeptides encoded by this exon from shark and mouse are 86 and 84 amino acids long, respectively. These polypeptides are overall 59% identical and include a region (residues 41-75 in shark and 39-73 in mouse) that is 89% identical between the two species. A primary sequence analysis showed that each of these polypeptides contains an N-glycosylation site, phosphorylation sites for Ca2+/calmodulin-dependent protein kinase, protein kinase C and casein kinase II, and partial ATP- and GTP-binding sites. The shark polypeptide also contains a phosphorylation site for proline-directed protein kinase. These observations are consistent with the notion that the intricate structure and regulation of the Golli-mbp gene complex arose during vertebrate evolution within a common ancestor to sharks and mammals.
J Mol Neurosci 1993
PMID:The structural complexities of the myelin basic protein gene from mouse are also present in shark. 752 2

The segregation of proteins to specific cellular membranes is recognized as a common phenomenon. In oligodendrocytes of the central nervous system, localization of certain proteins to select regions of the plasma membrane gives rise to the myelin membrane. Whilst the fundamental structure and composition of myelin is well understood, less is known of the mechanisms by which the constituent proteins are specifically recruited to those regions of plasma membrane that are forming myelin. The two principal proteins of myelin, the myelin basic protein and proteolipid protein, differ greatly in character and sites of synthesis. The message for myelin basic protein is selectively translocated to the ends of the cell processes, where it is translated on free ribosomes and is incorporated directly into the membrane. Proteolipid protein synthesized at the rough endoplasmic reticulum, processed through the Golgi apparatus, and presumably transported via vesicles to the myelin membrane. This review examines the mechanisms by which these two proteins are targeted to the myelin membrane.
Mol Membr Biol
PMID:Mechanisms of myelin basic protein and proteolipid protein targeting in oligodendrocytes (review). 752 97

The signal transduction initiated by the human cytokine interleukin-8 (IL-8), the main chemotactic cytokine for neutrophils, was investigated and found to encompass the stimulation of protein kinases. More specifically, IL-8 caused a transient, dose and time dependent activation of a Ser/Thr kinase activity towards myelin basic protein (MBP) and the MBP-derived peptide APRTPGGRR patterned after the specific concensus sequence in MBP for ERK enzymes. The activated MBP kinase was furthermore identified as an extracellular signal regulated kinase (ERK1) based on several criteria such as substrate specificity, molecular weight, activation-dependent mobility shift, and recognition by anti-ERK antibodies. For comparison, the chemotactic response of neutrophils to a stimulus of bacterial origin (fMet-Leu-Phe or fMLP) was also examined and found to involve the activation of a similar ERK enzyme. The present data clearly indicate that in terminally differentiated, non-proliferating human cells, the MBP kinase/ERK activity can serve other purposes than mitogenic signaling, and that processes such as chemotaxis, induced by bacterial peptides as well as by human cytokines like IL-8, involve the regulation of ERK enzymes.
Mol Cell Biochem 1993 Nov
PMID:Interleukin-8 activates microtubule-associated protein 2 kinase (ERK1) in human neutrophils. 752 47

Affinity-purified major histocompatibility complex (MHC) class II molecules are known to bind antigenic peptides in vitro. The percentage of MHC class II molecules occupied with such peptides is usually very low and varies significantly depending upon the sequence and size of a given antigenic peptide. The present study describes a method by which complete saturation of affinity-purified MHC class II with antigenic peptide can be achieved by simply incubating purified MHC class II molecules at neutral pH in the presence of several 100-fold molar excess of antigenic peptide. Complexes of human HLA-DR2 and a peptide analog from human myelin basic protein MBP (83-102)Y83 were selected for this study. The on-rate kinetic results showed saturation of MHC class II occupancy at 300-500-fold molar excess peptide concentrations. The specificity of the MBP (83-102)Y83 peptide binding to HLA-DR2 at higher peptide concentration was demonstrated by incubating an equivalent amount of another epitope from myelin basic protein [MBP (1-14) peptide] as well as by competitive binding assays. The quantitation of bound peptide was carried out using biotinylated-MBP (83-102)Y83 peptide which showed 100-125% occupancy of HLA-DR2 with a recovery of 100%. The presence of a single peptide entity in purified complexes was confirmed by reverse-phase narrowbore HPLC analysis of the acid extracted supernatant and by mass spectrometry analysis. Two-dimensional gel electrophoresis (IEF/SDS) of purified HLA-DR2 and DR2.MBP (83-102)Y83 complexes showed the absence of various endogenous polypeptides in 100% loaded complexes. These results demonstrate that higher peptide concentrations can be useful in generating MHC class II-peptide complexes of defined composition. Such complexes of MHC class II occupied with a single peptide may have significant clinical relevance for antigen-specific therapy of various autoimmune diseases and may provide better understanding of MHC-peptide-TCR interactions.
Mol Immunol 1994 Oct
PMID:Antigenic peptide binding to MHC class II molecules at increased peptide concentrations. 752 70

To assess the distribution of insulin-like growth-factor-related proteins during autoimmune CNS demyelination and remyelination, experimental autoimmune encephalomyelitis was produced by injecting Lewis rats with an emulsion containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia and incontinence were observed in some animals. From 8-40 days postinoculation (dpi), spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP mRNAs were increased in these lesions and transcripts encoding myelin basic protein (MBP) were greatly reduced. Large lesions with extensive demyelination were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi. MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin regenerating myelin sheaths were found morphologically. Astrocytes, identified by their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2 mRNA and peptide in normal controls; their levels were significantly higher 14 dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels were also elevated around lesions and in some normal-appearing areas of WM and GM 14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP-positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization and immunocytochemistry as well as by double immunostaining. Coexpression of IGF-I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time. This suggests that during lesion progression and recovery, astrocytic expression of IGF-I-related peptides may reduce immune-mediated myelin injury. We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons.
Mol Cell Neurosci 1994 Oct
PMID:Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. 752 31

The box I and II motif located within the promoter of the myelin basic protein gene contains a simian virus 40 T-antigen-binding site, a MyoD/E2a-binding site, and a glucocorticoid receptor-binding site. We have found proteins within nuclear extracts from adult mouse brain, rat embryonic cerebral cortex in culture, and a mouse oligodendrocyte-like cell line that bind to a 32P-labeled synthetic DNA fragment containing the sequences of the box I and II motif. Three major complexes (A, B, and C) were seen in gel-shift assays. Only complexes A and B were competed out by the unlabeled box I and II fragment or by another synthetic DNA fragment that also contains sequences similar to a glucocorticoid receptor-binding site. Therefore, complexes A and B were thought to be specific. The expression pattern of the proteins responsible for the formation of these complexes was also assessed during development in mouse brain.
J Mol Neurosci 1994
PMID:Box I and II motif from myelin basic protein gene promoter binds to nuclear proteins from rodent brain. 753 95

Based on a suspected role of the immune system in the pathophysiology of Alzheimer's disease (AD) and the new discoveries of neuroimmune networks, the investigation of certain neuroimmune markers was performed in AD patients, healthy controls, and disease controls. In agreement with our previous immunological research on AD, the assessment of additional immune parameters revealed abnormalities of both cellular and humoral immunity in several AD patients. These include: 1. Enhanced production of cytokines, such as interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6); 2. Increase plasma level of CD8-positive lymphocyte derived soluble CD8 (sCD8) antigen; and 3. Increased incidence of autoantibodies to brain myelin basic protein (MBP) and thymic cells. As analyzed by flow cytometry and enzyme immunoassay, the peripheral blood immunocytes from AD patients showed a significant increase in the expression of the brain-derived S-100 protein. In the cell proliferation assay, the blood immunocytes from healthy subjects responded to stimulation with beta-amyloid protein (beta AP), but this response was absent in AD patients. The initial results of our research suggest that the studies of specific markers of the neuroimmune axis may be potentially important for the new development of diagnostic and therapeutic strategies for AD.
Mol Neurobiol
PMID:Studies of neuroimmune markers in Alzheimer's disease. 753 89


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