Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RYK is an atypical orphan receptor tyrosine kinase that lacks detectable kinase activity. Nevertheless, using a chimeric receptor approach, we previously found that RYK can signal via the mitogen-activated protein kinase pathway. Recently, it has been shown that murine Ryk can bind to and be phosphorylated by the ephrin receptors EphB2 and EphB3. In this study, we show that human RYK associates with EphB2 and EphB3 but is not phosphorylated by them. This association requires both the extracellular and cytoplasmic domains of RYK and is not dependent on activation of the Eph receptors. It was also previously shown that AF-6 (afadin), a PDZ domain-containing protein, associates with murine Ryk. We show here that AF-6 does not bind to human RYK in vitro or in vivo. This suggests that there are significant functional differences between human and murine RYK. Further studies are required to determine whether RYK modulates the signaling of EphB2 and EphB3.
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PMID:RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and EphB3 but does not interact with AF-6. 1195 17

Nucleus magnocellularis (NM) in the avian auditory brainstem receives auditory input from nerve the VIIIth and projects bilaterally to nucleus laminaris (NL). This projection preserves binaural segregation in that ipsilateral NM projects to dorsal dendrites of NL and contralateral NM projects to ventral dendrites of NL. We have begun to examine the molecular signals that influence segregation of inputs onto discrete regions of NL cells. We previously showed that the Eph receptor, EphA4, is expressed selectively in the dorsal NL neuropil from embryonic day (E) 9 to E11, when NM axons grow into the NL neuropil. This asymmetric distribution suggests that EphA4 acts as a guidance molecule during binaural segregation. We report here on the developmental changes in the expression of two other Eph receptors, EphB2 and EphB5, and two ligands, ephrin-B1 and ephrin-B2, in the chick auditory brainstem. These proteins are expressed in the auditory nuclei during the maturation of the NM-NL projection. EphB2, EphB5, and ephrin-B1 are expressed in dorsal and ventral NL neuropil and at the midline of the brainstem at E10-E12. At this age, ephrin-B2, a ligand for EphB receptors and for EphA4, is expressed in NL cell bodies and NM-NL axons. The expression of these proteins diminishs in the posthatch ages examined. These results suggest that several members of the Eph family are involved in maturation of the nuclei and their projections. Moreover, ephrin-B2 in growing axons may interact with the asymmetrically expressed EphA4 during the establishment of binaural segregation.
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PMID:Expression of EphB receptors and EphrinB ligands in the developing chick auditory brainstem. 1220 9

The German bone marrow donor center (DKMS) hasrecruited over 732 500 donors during the first 9 years of its existence. Initially, donors were typed for HLA-A and B, and DR typing was only done on request for a patient-initiated search. In 1994, a project was started which led to the donor center-initiated DR typing (DCI-DRT) of >35,000 donors. These donors were selected by donor-specific criteria (age, sex, height and weight) and according to HLA-A and B phenotypes. The latter was done to avoid unnecessary DR typing of the most common A, B phenotypes With a follow up of >6 years, this strategy has led to a number of confirmatory typings (CT) (n=4588) and stem cell harvests (n=568), which is at least comparable to those ensuing after patient-initiated HLA-DR typing (126 000 DR typings, 8,213 CTs, 888 resulting in stem-cell donation). DCI-DRT seems to be a cost-effective strategy which may help to reduce search times and improve search outcome, and improve the overall efficiency of donor center operations
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PMID:Approaches to managing volunteer marrow donor registry HLA data. Algorithms for directing donor center-initiated HLA-DR typing of selected donors. 1236 Oct 95

Attention has been implicated in postural control and other tasks requiring sensory integration. The purpose of this study was to investigate the role of attention in sensory-motor processing of vestibular and combined visual-vestibular information during seated rotations using a dual-task interference approach. We hypothesized that auditory information processing would be influenced by concurrent visual-ocular, vestibulo-ocular, or combined visual-vestibulo-ocular processing. We further hypothesized that the effect would be greater in older subjects. Twenty older subjects (10 women, 10 men, 69.3+/-3.2 years) and 20 young subjects (10 women, 10 men, 23.5+/-2.9 years) were asked to perform information-processing tasks while they underwent several types of vestibular, visual-vestibular, and ocular motor paradigms. The information-processing tasks were: (1) an auditory simple reaction-time task (SRT), (2) an auditory go-no-go (disjunctive) reaction-time task (DRT), and (3) an auditory forced-choice task (CRT). The visual-vestibular-ocular motor conditions included: (1) no movement/darkness (NO), (2) no movement/fixation (FIX), (3) no movement/pursuit (P), (4) earth-vertical axis rotation (EVAR) in darkness, (5) EVAR with fixation (E-FIX), (6) off-vertical axis rotation (OVAR) in darkness, and (7) OVAR with fixation (O-FIX). Results showed that older subjects had longer reaction times for all combinations of stimulus condition and reaction-time task compared with young subjects. Compared with the NO baseline, reaction times during EVAR were longer for young and older subjects and during OVAR were longer for the young subjects. For FIX and P, the reaction times during P exceeded those during FIX and during NO for both groups. For E-FIX and O-FIX, reaction times did not differ from those during EVAR and OVAR. The interference with information processing by concurrent vestibular stimulation in the dark may be based upon cortical inhibition of auditory processes by vestibular stimulation. Eye movements induced by EVAR showed an increased phase lead during reaction-time tasks, suggesting altered vestibulo-ocular reflex (VOR) dynamics, possibly based on cerebellar-mediated changes in velocity storage. Since fixation of a head-fixed visual target did not add to the effect of rotation in the dark, a further implication of our results is that VOR-fixation while performing a concurrent information-processing task may be accomplished primarily by VOR suppression rather than by VOR cancellation.
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PMID:Visual-vestibular stimulation interferes with information processing in young and older humans. 1292 Apr 95

Three studies describe the development and validation of a new procedure (AVLTX) to detect inadequate effort or malingering by adding 60-min delayed recall/recognition trials and identifying "impaired" memory performances that are highly inconsistent with performances of brain-damaged (BD) individuals. In Study I, AVLTX performances of 25 probable malingerers (PMs) were compared with those of 43BD and 40 psychiatric patients (PSYs). Seven inconsistencies were identified and converted to scaled inconsistency scores, yielding the exaggeration index (EI). Study II reported cross-validation in an independent sample of 34 PM, 70BD and 89 PSY, showing sensitivity of 0.59 and specificities of 0.97 (BD) and 0.92 (PSY). Study III compared the diagnostic accuracy of the EI with two well-established effort assessment paradigms, exemplified by the RMTand DRT (a symptom validity test). The RMT showed excellent sensitivity and poor specificity; the DRT showed poor sensitivity and excellent specificity; the EI showed good sensitivity and excellent specificity. Adding a second delayed trial to list-learning tests can be a time-efficient procedure to detect inadequate effort.
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PMID:Detecting poor effort and malingering with an expanded version of the Auditory Verbal Learning Test (AVLTX): validation with clinical samples. 1497

The identification of tumor-suppressor genes in solid tumors by classical cancer genetics methods is difficult and slow. We combined nonsense-mediated RNA decay microarrays and array-based comparative genomic hybridization for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele. This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EPHB2. The DU 145 prostate cancer cell line, originating from a brain metastasis, carries a truncating mutation of EPHB2 and a deletion of the remaining allele. Additional frameshift, splice site, missense and nonsense mutations are present in clinical prostate cancer samples. Transfection of DU 145 cells, which lack functional EphB2, with wild-type EPHB2 suppresses clonogenic growth. Taken together with studies indicating that EphB2 may have an essential role in cell migration and maintenance of normal tissue architecture, our findings suggest that mutational inactivation of EPHB2 may be important in the progression and metastasis of prostate cancer.
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PMID:Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. 1534 Apr 30

This article provides psychometric analysis of the performance of nursing students on categories of client needs (CN) and nursing process (NP) measured by the NLN Diagnostic Readiness Test (NLN-DRT) for RN licensure. While analyses of items and number-right score performance with NLN tests are well documented, the analysis of proficiency on categories that organize items at the conceptual level is limited to reporting basic classical statistics (e.g., proportion of correct scores and percentiles). The psychometric analysis of proficiency on categories of CN and NP in this article is based on item response theory and takes into account that the binary scores on these 2 categories (1 = mastered, 0 = nonmastered) are obtained through summative standardized scoring and not through direct responses of examinees. NLN-DRT data for a local population of 646 students enrolled in an NLN accredited associate degree program was obtained 3 weeks prior to graduation. This article illustrates the application of IRT using the Rasch Model and the 2-parameter logistic model in a method of psychometric analysis that deals with proficiency on conceptual categories and provides measurement feedback to nursing educators for curriculum (or instruction) intervention in a specific educational context. Among the components of such feedback provided in this article are: (a) difficulty, discrimination, and characteristic curves of CN and NP categories, (b) performance patterns by level of success on each category, and (c) domain scores by ability levels for the population of nursing students. The Rasch Model, which was calculated using RASCAL, did not fit the data with the categories of CN or NP at the .05 level of statistical significance. However, the 2-parameter logistic model fit the data with both CN and NP categories while using the XCALIBRE computer program. The IRT approach used in this article demonstrated some measurement perspectives on linking an instrument's conceptual base to theory in the context of nursing education, and provide valuable measurement feedback for improving the quality of curriculum and teaching in institutions that use the NLN-DRT in their assessment practice.
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PMID:Psychometric analysis of performance on categories of client needs and nursing process with the NLN Diagnostic Readiness Test. 1563 77

The cochleovestibular ganglion of the chick differentiates at early embryonic stages as VIIIth nerve axons enter the brainstem. The tonotopic organization of the auditory portion of the VIIIth nerve can be discerned at the time axons initially reach their brainstem targets. The mechanisms underlying this early organization are not known. Eph receptor tyrosine kinases and their ligands, the ephrins, have a demonstrated role in guiding axons to topographically appropriate locations in other areas of the nervous system. In order to begin to test whether Eph proteins have a similar role in the auditory system, we investigated the tonotopic expression of several Eph receptors and ephrins in the VIIIth nerve during embryonic ages corresponding to the initial innervation of the auditory brainstem. Expression patterns of EphA4, EphB2, EphB5, ephrin-A2, and ephrin-B1 were evaluated immunohistochemically at embryonic days 4 through 10. Protein expression was observed in the cochlear ganglion and VIIIth nerve axons at these ages. EphB5, ephrin-A2, and ephrin-B1 were expressed throughout the nerve. EphA4 and EphB2 had complementary expression patterns within the nerve, with EphA4 expression higher in the dorsolateral part of the nerve and EphB2 expression higher in the ventromedial part of the nerve. These regions may correspond to auditory and vestibular components, respectively. Moreover, EphA4 expression was higher toward the low-frequency region of both the centrally and peripherally projecting branches of cochlear ganglion cells. Regional variation of Eph protein expression may influence the target selection and topography of developing VIIIth nerve projections.
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PMID:Differential expression of Eph receptors and ephrins in the cochlear ganglion and eighth cranial nerve of the chick embryo. 1566 77

Mammalian RYK is a receptor related to tyrosine kinase without detectable catalytic activity. We have previously reported that rat RYK is dominantly expressed in neural progenitor cells and mature neurons in the developing central nervous system. Mouse RYK has been found to bind to EphB2/B3 receptors, which have diverse functions during development. In this study, we demonstrated that RYK, EphB2, EphB3, ephrinB1, and ephrinB2 are expressed in embryonic brain. In vitro analysis using COS-7 cells revealed binding between rat RYK and EphB3, and that the RYK deletion mutant without extracellular leucine-rich motifs lacked this binding ability. To investigate the function of RYK in vivo, embryonic cortical slice cultures were analyzed after electroporation of expression plasmids for RYK or its deletion mutants. The results showed that overexpression of RYK suppressed cell migration from the ventricular zone to the pial surface, however, overexpression of the RYK deletion mutant without leucine-rich motifs had no effect on cell migration. These results suggest that RYK regulates cell migration during mammalian cortical development through the binding to Eph receptors.
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PMID:Receptor related to tyrosine kinase RYK regulates cell migration during cortical development. 1579 3

The pathogenesis of metastasis depends on multiple favorable interactions of tumor cells with host homeostatic mechanisms. Interruption of one or more of these interactions can lead to the inhibition or eradication of cancer metastases. For many years, all efforts to treat cancer concentrated on the inhibition of growth or the destruction of tumor cells. A strategy of both eradication of tumor cells (e.g. by chemotherapy and immunotherapy) and modulation of the host microenvironment (e.g. tumor vasculature and hypoxia) is an additional, relatively novel approach to cancer treatment. Recent advances in our understanding of the biological basis of cancer metastasis open up unprecedented opportunities for translating basic research to clinical treatment of cancer. This research includes the unraveling of the genetic make-up of tumors and genome-wide expression analyses, thereby identifying many potential targets for therapy. Drugs acting on tumor cells which have a metastasis-prone mutational or expression status (by classical or targeted chemotherapy) as well as drugs affecting host-mediated survival pathways must be combined in order to create therapeutic synergy. Therapeutic maneuvers may target receptor tyrosine kinases (EGFR, VEGFR, FGFR), chemokines or G-protein-coupled receptors (CXCR4, CXCR2, EphB2), hypoxia-inducible factor (HIF), and signaling pathways (c-Src, PI3K, Akt, chaperon complexes) in tumor cells. Moreover, stromal and immunological cells and their cytokines coordinate critical pathways that exert important roles in the ability of tumors to invade and metastasize, thus suppressive cytokines (IL-6 and IL-10) and neutralizing specific antibodies might subvert conditions for metastasis.
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PMID:Metastases and their microenvironments: linking pathogenesis and therapy. 1609 51


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