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At least 613 records · Page 34Linked to original sources
PubMed1982

Interstitial de novo deletion of the long arm of chromosome 5: mapping of 5q bands associated with particular malformations.

A new case of interstitial deletion of the long arm of one chromosome No. 5 (q13 leads to q22) is described. The girl shows mental retardation, severe hypotonia, dysmorphic facies and peculiar dermatoglyphics. The relationship between partial trisomies and partial monosomies of 5q chromosomal segments and associated clinical features is discussed. It seems possible to draw a rough phenotypic map of the long arm of chromosome 5 (5q), correlating observed malformations and phenotypic features with specific chromosomal regions.

Abnormalities, Multiple↗
PubMed1988

Estramustine binds MAP-2 to inhibit microtubule assembly in vitro.

We have investigated the ability of estramustine to bind to rat brain microtubule-associated proteins (MAPs) and purified MAP-2 in vitro. [3H]estramustine's relative affinity for tubulin and MAPs was assessed by gel filtration chromatography, immunoprecipitation and binding assays. Scatchard analysis demonstrated a specific affinity of the drug for MAP-2. Calculations from kinetic parameters and non-linear regression analysis gave a Kd of 15 microM, and a Bmax of 3.4 x 10(-7)M ml-1. Extrapolation of this value suggested that each MAP-2 molecule binds approximately 20 molecules of estramustine. Microtubule assembly studies and SDS-polyacrylamide gel electrophoresis revealed that at 20-60 microM levels, estramustine inhibited the association of MAPs with taxol microtubules. Turbidity (A350) studies further demonstrated that 20-60 microM-estramustine inhibited MAP-2-driven tubulin assembly and produced microtubule disassembly. Electron-microscopic studies confirmed the centrifugation and turbidity results. The data demonstrated that estramustine can bind MAPs and MAP-2 specifically, thereby inhibiting microtubule assembly.

Animals↗
PubMed1992

Identification of an activator of the microtubule-associated protein 2 kinases ERK1 and ERK2 in PC12 cells stimulated with nerve growth factor or bradykinin.

Treatment of PC12 pheochromocytoma cells with nerve growth factor (NGF) or bradykinin leads to the activation of extracellular signal-regulated kinases ERK1 and ERK2, two isozymes of microtubule-associated protein 2 (MAP) kinase that are present in numerous cell lines and regulated by diverse extracellular signals. The activation of MAP kinase is associated with its phosphorylation on tyrosine and threonine residues, both of which are required for activity. In the present studies, we have identified a factor in extracts of PC12 cells treated with NGF or bradykinin, named MAP kinase activator, that, when reconstituted with inactive MAP kinase from untreated cells, dramatically increased MAP kinase activity. Activation of MAP kinase in vitro by this factor required MgATP and was associated with the phosphorylation of a 42- (ERK1) and 44-kDa (ERK2) polypeptide. Incorporation of 32P into ERK1 and ERK2 occurred primarily on tyrosine and threonine residues and was associated with a single tryptic peptide, which is identical to one whose phosphorylation is increased by treatment of intact PC12 cells with NGF. Thus, the MAP kinase activator identified in PC12 cells is likely to be a physiologically important intermediate in the signaling pathways activated by NGF and bradykinin. Moreover, stimulation of the activator by NGF and bradykinin suggests that tyrosine kinase receptors and guanine nucleotide-binding protein-coupled receptors are both capable of regulating these pathways.

Animals↗
PubMed1995

Ste5: a meeting place for MAP kinases and their associates.

Growth and differentiation of the budding yeast Saccharomyces cerevisiae is regulated by six functionally distinct but structurally similar MAP kinase cascades. Three of the protein kinases in the cascade that regulates G1-phase arrest and mating have recently been shown to form a multikinase complex with a LIM-domain-containing protein called Ste5. These studies implicate Ste5 as a tethering protein that physically links protein kinases operating sequentially in a cascade. The significance of this complex for the regulation and specificity of signal transduction is explored in this review.

Journal Article↗
PubMed2004

Genome-wide association study identifies ITGB3 as a QTL for whole blood serotonin.

Serotonin has been implicated in common disorders involving the central nervous, gastrointestinal, cardiovascular, and pulmonary systems. We describe the first genome-wide screen to identify quantitative trait loci (QTLs) influencing whole blood serotonin in 567 members of a single large pedigree, using a novel association-based mapping approach. We identified an association between the beta3 integrin (ITGB3) Leu33Pro polymorphism on 17q21 and whole blood serotonin levels (P-value = 9.8 x 10(-5)). This variant explained the evidence for linkage in this region when included as a covariate in the linkage analysis (change in LOD from 1.87 to 0.16), indicating that ITGB3 may be an important serotonin QTL.

Female↗
PubMed2001

Mrnp41 (Rae 1p) associates with microtubules in HeLa cells and in neurons.

Mrnp41 (hRae1p) is an evolutionarily highly conserved protein, which is a potential component of mRNP particles and plays a role in nuclear mRNA export. The protein is mainly localized at the nuclear pore complex, but is also associated with distinct nuclear domains and with a meshwork of numerous small particles in the cytoplasm (Kraemer and Blobel (1997): Proc. Natl. Acad. Sci. USA 91, 1519-1523). We show that the cytoplasmic pattern of mrnp41 is sensitive to treatment with the microtubule (MT)-depolymerizing drug nocodazole which causes disappearance of mrnp41 from the cell periphery and concentration around the nucleus. By immunofluorescence we demonstrate that mrnp41 colocalizes with MT in HeLa cells and displays an MT-like distribution in cultured neurons. Association of mrnp41 with MT is further demonstrated by copurification with MT from pig brain throughout several steps of polymerization and depolymerization. Separation of MT-associated proteins (MAPs) by phosphocellulose (PC) chromatography showed copurification of mrnp41 with MAPs. These data show an association of mrnp41 with MT and, moreover, demonstrate that an intact MT system is necessary for dispersion of mrnp41-containing particles to the cellular periphery. The essential role of mrnp41 in spindle pole separation and cell cycle progression may also be related to its ability to bind to MTs.

Animals↗
PubMed1995

Mapping disease genes: family-based association studies.

With recent rapid advances in mapping of the human genome, including highly polymorphic and closely linked markers, studies of marker associations with disease are increasingly relevant for mapping disease genes. The use of nuclear-family data in association studies was initially developed to avoid possible ethnic mismatching between patients and randomly ascertained controls. The parental marker alleles not transmitted to an affected child or never transmitted to an affected sib pair form the so-called AFBAC (affected family-based controls) population. In this paper, the theoretical foundation of the AFBAC method is proved for any single-locus model of disease and for any nuclear family-based ascertainment scheme. In a random-mating population, when there is a marker association with disease, the AFBAC population provides an unbiased estimate of the overall population (control) marker alleles when the recombination fraction (theta) between the marker and disease genes is sufficiently small that it can be taken as zero (theta = 0). With population stratification, only marker associations present in the subpopulations will be detected with family-based analyses. Of more importance, however, is the fact that, when theta not equal to 0, differences between transmitted parental (patient) marker allele frequencies and non- or never-transmitted parental marker allele frequencies (implying a marker association with disease) can only be observed for marker genes linked to a disease gene (theta < 1/2). Thus, associations of unlinked marker loci with disease at the population level, caused by population stratification, migration, or admixture, are eliminated. This validates the use of family-based association tests as an appropriate strategy for mapping disease genes.

Chromosome Mapping↗
PubMed1999

GFP chimeras of E-MAP-115 (ensconsin) domains mimic behavior of the endogenous protein in vitro and in vivo.

E-MAP-115 (ensconsin) is a microtubule-associated protein (MAP) abundant in carcinoma and other epithelia-derived cells. We expressed chimeras of green fluorescent protein (GFP) conjugated to ensconsin's N-terminal MT-binding domain (EMTB), to study distribution, dynamics, and function of the MAP in living cells. We tested the hypothesis that behavior of expressed GFP-EMTB accurately matched behavior of endogenous ensconsin. Like endogenous MAP, GFP-EMTB was associated with microtubules in living or fixed cells, and microtubule association of either molecule was impervious to extraction with nonionic detergents. In cell lysates both GFP-EMTB and endogenous ensconsin were dissociated from microtubules by identical salt extraction conditions, and both molecules remained bound to a calcium-stable subset of Taxol-stabilized microtubules. These data show that microtubule association of ensconsin was affected neither by the absence of domains other than its microtubule-binding domain, nor by the presence of appended GFP. We took advantage of this finding to generate constructs in which additional GFP moieties were attached to EMTB, to obtain a more intensely fluorescent reporter of in vivo MAP binding. We show here that expression of chimeric proteins consisting of five GFP molecules attached to a single EMTB molecule produces brightly labeled microtubules without compromising the behavior of the MAP or the microtubules to which it is attached. Thus, we have demonstrated the utility of chimeric proteins containing GFP multimers as authentic reporters of ensconsin distribution and dynamics; expression of these GFP-EMTB chimeric molecules also provides a non-perturbing label of the microtubule system in living cells.

Animals↗
PubMed1996

Plasmacytoma-associated neuronal glycoprotein, Pang, maps to mouse chromosome 6 and human chromosome 3.

A new member of the immunoglobulin/fibronectin superfamily of adhesion molecules, Pang (plasmacytoma-associated neuronal glycoprotein), was recently isolated from a plasmacytoma. In previous studies, Pang was found to be normally expressed in the brain and ectopically activated by intracisternal A-type particle long terminal repeats in plasmacytomas. In this study, Pang was initially mapped to mouse Chr 6 by somatic cell hybrid analysis and further positioned on the chromosome between Wnt7a and Pcp1. Southern blot analysis of human-rodent somatic cell hybrids together with predictions from the mouse map location indicate that human PANG is located at 3p26.

Animals↗
PubMed2025

FINEMAP-miss: fine-mapping genome-wide association studies with missing genotype information.

MOTIVATION: The most informative genome-wide association studies (GWAS) are meta-analyses that have combined multiple studies to increase the GWAS sample size. Statistical fine-mapping is a key downstream analysis of GWAS to jointly evaluate the probability of causality of all variants in a genomic region of interest. Current fine-mapping methods are miscalibrated in the meta-analysis setting due to variation in sample size across the variants. RESULTS: We introduce FINEMAP-miss, a new fine-mapping method that extends the FINEMAP model to account for variant-specific missingness. We show that FINEMAP-miss is well-calibrated in meta-analysis simulations where the standard fine-mapping fails. Compared to the summary statistics imputation approach, FINEMAP-miss provides clear improvement when the causal variants have low imputation information or when the sample size or complexity of the meta-analysis setting increase. We successfully apply FINEMAP-miss on a breast cancer GWAS meta-analysis where neither the standard fine-mapping nor the summary statistics imputation are applicable. AVAILABILITY: An open source implementation of FINEMAP-miss as an R package ("finemapmiss") is available at https://github.com/JoonasKartau/finemapmiss. The archived version of FINEMAP-miss used for this publication can be found on Zenodo at https://doi.org/10.5281/zenodo.17492622. SUPPLEMENTARY INFORMATION: is available at the journal's web site.

Genome-Wide Association Study↗
PubMed1995

Pancreatic tau related maps: biochemical and immunofluorescence analysis in a tumoral cell line.

In the present study, we report the existence of four tau-related microtubule-associated proteins (MAPs) of 48, 50, 55 and 58 kDa in a pancreatic exocrine cell line (AR4-2J). Using immunofluorescence, we demonstrate that these tau-related MAPs are associated with microtubules in AR4-2J cells. That colocalization is particularly striking on microtubules bundles in cellular extensions and is the first evidence for tau-related MAPs colocalization with microtubules in non-neuronal cells. As it has been often discussed for neuronal tau, the localization of tau-related proteins in AR4-2J cells suggests that these proteins may be involved in microtubule bundling.

Animals↗
PubMed2000

Toward neuroanatomical models of analogy: a positron emission tomography study of analogical mapping.

Several brain regions associated with analogical mapping were identified using (15)O-positron emission tomography with 12 normal, high intelligence adults. Each trial presented during scanning consisted of a source picture of colored geometric shapes, a brief delay, and a target picture of colored geometric shapes. Analogous pictures did not share similar geometric shapes but did share the same system of abstract visuospatial relations. Participants judged whether each source-target pairing was analogous (analogy condition) or identical (literal condition). The results of the analogy-literal comparison showed activation in the dorsomedial frontal cortex and in the left hemisphere; the inferior, middle, and medial frontal cortices; the parietal cortex; and the superior occipital cortex. Based on these results as well as evidence from relevant cognitive neuroscience studies of reasoning and of executive working memory, we hypothesize that analogical mapping is mediated by the left prefrontal and inferior parietal cortices.

Adult↗
PubMed1996

Cellular expression of MAP 2 kinase in rat brain.

The cellular localization of microtubule-associated protein (MAP) 2 kinase mRNA in rat brain was examined by in situ hybridization histochemistry using a synthetic oligonucleotide probe. MAP 2 kinase was expressed in both neuronal and non-neuronal cells. Areas of high density of mRNA label by the MAP 2 kinase probe appeared to be associated with high cellular packing density. Thus, MAP 2 kinase expression was particularly high in regions such as the locus coeruleus, the piriform cortex, the dentate gyrus granule cell layer, pyramidal cells of the hippocampus, the mitral cells of the olfactory bulb, and the large motor neurons of the V and VII nerves. This apparent ubiquitous distribution suggests an important role of MAP 2 kinase in the cellular functions in most cells of the adult brain.

Animals↗
PubMed1991

Microtubule destabilization by cdc2/H1 histone kinase: phosphorylation of a "pro-rich region" in the microtubule-binding domain of MAP-4.

Microtubule-associated protein-4 (MAP-4), a major MAP in proliferating cells, consists of a microtubule-binding domain and a projection domain protruding from the microtubule wall. The former contains a Pro-rich region and an assembly-promoting (AP) sequence region which is common to the neuron-specific MAPs, MAP-2 and tau1. In this paper, we describe the phosphorylation of the Pro-rich region of MAP-4 and the suppression of its assembly-promoting activity by cdc2/H1 histone kinase. This inactivation of MAP-4 may cause disassembly of the interphase microtubular network at the end of the G2 phase of the cell cycle.

Amino Acid Sequence↗
PubMed1988

[Application of monoclonal antibodies to cancer therapy: idiotype mapping of monoclonal antibodies to tumor-associated antigens].

Polyclonal and monoclonal anti-idiotypic antibodies were prepared against several monoclonal antibodies which reacted with high molecular-weight melanoma-associated antigens. Idiotype mapping was proposed from the serological data obtained from these anti-idiotypic antibodies. This mapping will be of use for applying the anti-idiotypic monoclonal antibodies for cancer therapy.

Antibodies, Monoclonal↗
PubMed2001

Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys.

While the pathophysiological changes induced by the loss of dopamine innervation in the basal ganglia by Parkinson's disease (PD) are well studied, little is known about functional changes in the neural circuitry of this area during normal aging. Here we report the first survey of age-associated changes in the basal ganglia of behaviorally characterized, awake rhesus monkeys, using pharmacological MRI to map responses to dopaminergic stimulation. Apomorphine, a mixed D(1)/D(2) dopamine receptor agonist, evoked little change in the substantia nigra (SN) of aged animals while significantly reducing activation in young adult monkeys. Compared to young animals, both apomorphine and d-amphetamine (which increases synaptic dopamine levels) significantly increased activation of the aged rhesus globus pallidus externa (GPe). In addition, the aged animals showed decreased activity in the putamen in response to d-amphetamine administration. Although the responses in the SN and putamen of the aged monkeys differed from those in animal models of PD, the apomorphine-evoked activation of their GPe corresponded with apomorphine-induced increases in neuronal activity seen in Parkinson's patients and animal models. Given the major role of the GPe in regulating motor behavior, the altered responses in the aged GPe may contribute significantly to the motor slowing and movement dysfunctions characterizing advanced age.

Aging↗
PubMed1992

A high molecular mass phosphoprotein defined by a novel monoclonal antibody is closely associated with the intermicrotubule cross bridges in the Trypanosoma brucei cytoskeleton.

The main component of the cell body cytoskeleton of Trypanosoma brucei is the highly organised array of stable, subpellicular microtubules on the cytoplasmic face of the plasma membrane. Although several microtubule associated proteins (MAPs) have been shown to be associated with this array, the mechanisms by which individual microtubules interact with one another and with the membrane are still largely undetermined. In this study we have used the T. brucei cytoskeleton as a complex immunogen for the production of monoclonal antibodies to define novel cytoskeletal antigens. Screening by immunofluorescence enabled the selection of an antibody, WCB-1, which detects an antigen associated specifically with the subpellicular microtubules and not with the flagellum microtubules. The antigen (WCB210) was shown to have a relative molecular mass of 210,000 by western blotting. Immunogold studies showed the epitope to be located on the membrane-facing side of the subpellicular cage; it appears to be closely associated with the cross-bridges lying between the microtubules. Unlike many MAPs this protein was shown not to be heat stable and is predicted to be a roughly globular monomer. Even though WCB210 is a very minor component of the cytoskeleton it is heavily phosphorylated. It is possible that this protein is involved in regulation of the subpellicular microtubule crossbridges by interaction with other proteins.

Animals↗
PubMed1983

Length and appearance of projections on neuronal microtubules in vitro after negative staining: evidence against a crosslinking function for MAPs.

The length and appearance of microtubule-associated proteins (MAPs) on microtubules reconstituted in vitro have been investigated by the negative-staining technique. We found that uranyl acetate (UA) causes the normally extended MAPs on microtubules to coil up into globular projections 7-10 nm in length. This perturbation occurred if the microtubules reacted with UA before they became adsorbed to the grid surface. If the microtubules were adsorbed to the grid surface before staining, the MAPs remained as extended, filamentous molecules, 35-40 nm in length. Glutaraldehyde also caused MAPs to coil into globular structures. In the altered, globular configuration, MAPs served to crosslink pairs of microtubules. In the normal filamentous configuration, MAPs were never seen to crosslink pairs of microtubules. Therefore, we concluded that MAPs do not function as crosslinking proteins between microtubules.

Animals↗