Adapter Molecule (adapter + molecule)

Distribution by Scientific Domains

Selected Abstracts

Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain

GLIA, Issue 2 2006
Huanyu Dou
Abstract The balance between astrocyte and microglia neuroprotection and neurotoxicity defines the tempo of neuronal dysfunction during HIV-1-associated dementia (HAD). Astrocytes maintain brain homeostasis and respond actively to brain damage by providing functional and nutritive neuronal support. In HAD, low-level, continuous infection of astrocytes occurs, but the functional consequences of thisinfection are poorly understood. To this end, human fetal astrocytes (HFA) and monocyte-derived macrophages (MDM) were infected with HIV-1DJV and HIV-1NL4-3 (neurotropic and lymphotropic strains respectively) and a pseudotyped Vesicular Stomatitis Virus (VSV/HIV-1NL4-3) prior to intracranial injection into the basal ganglia of severe combined immunodeficient mice. Neuropathological and immunohistochemical comparisons for inflammatory and neurotoxic activities were performed amongst the infected cell types at 7 or 14 days. HIV-1-infected MDM induced significant increases in Mac-1, glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, and proinflammatory cytokine RNA and/or protein expression when compared with HSV/HIV-1- and HIV-1-infected HFA and sham-operated mice. Levels of neuron-specific nuclear protein, microtubule-associated protein 2, and neurofilament antigens were reduced significantly in the brain regions injected with human MDM infected with HIV-1DJV or VSV/HIV-1. We conclude that HIV-1 infection of astrocytes leads to limited neurodegeneration, underscoring the early and active role of macrophage-driven neurotoxicity in disease. © 2006 Wiley-Liss, Inc. [source]

Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4

IMMUNOLOGY, Issue 2 2004
Eva M. Pålsson-McDermott
Summary An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS , Toll-like receptor 4 (TLR4) , but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88-like adapter (Mal), leads to the activation of nuclear factor-,B (NF-,B). A later response to LPS makes use of TIR-domain-containing adapter-inducing interferon-, (TRIF) and TRIF-related adapter molecule (TRAM), and leads to the late activation of NF-,B and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS. [source]

KIT and RAS signalling pathways in testicular germ cell tumours: new data and a review of the literature

N. C. Goddard
Summary Testicular germ cell tumours (TGCTs) are the leading cause of cancer deaths in young male Caucasians. Identifying changes in DNA copy number can pinpoint genes involved in tumour development. We defined the smallest overlapping regions of imbalance in TGCTs using array comparative genomic hybridization analysis. Novel regions, or regions which refined those previously reported, were identified. The expression profile of genes from 12p, which is invariably gained in TGCTs, and amplicons defined at 12p11.2-12.1 and 4q12, suggest KRAS and KIT involvement in TGCT and seminoma development, respectively. Amplification of these genes was not found in intratubular germ cell neoplasia adjacent to invasive disease showing these changes, suggesting their involvement in tumour progression. Activating mutations of RAS genes (KRAS or NRAS) and overexpression of KRAS were mutually exclusive events. These, correlations between the expression levels of KIT, KRAS and GRB7 (which encodes an adapter molecule known to interact with the KIT tyrosine kinase receptor) and other reported evidence reviewed here, are consistent with a role for activation of KIT and RAS signalling in TGCT development. In order to assess a role for KIT in seminomas, we modulated the level of KIT expression in TCam-2, a seminoma cell line. The likely seminomatous origin of this cell line was supported by demonstrating KIT and OCT3/4 overexpression and gain of 12p material. Reducing the expression of KIT in TCam-2 through RNA inhibition resulted in decreased cell viability. Further understanding of KIT and RAS signalling in TGCTs may lead to novel therapeutic approaches for these tumours. [source]

Nucleocytoplasmic protein traffic and its significance to cell function

GENES TO CELLS, Issue 10 2000
Yoshihiro Yoneda
In eukaryotic cells, cell functions are maintained in an orderly manner through the continuous traffic of various proteins between the cell nucleus and the cytoplasm. The nuclear import and export of proteins occurs through nuclear pore complexes and typically requires specific signals: the nuclear localization signal and nuclear export signal, respectively. The transport pathways have been found to be highly divergent, but are known to be largely mediated by importin ,-like transport receptor family molecules. These receptor molecules bind to and carry their cargoes directly or via adapter molecules. A small GTPase Ran ensures the directionality of nuclear transport by regulating the interaction between the receptors and their cargoes through its GTP/GDP cycle. Moreover, it has been recently elucidated how the transport system is involved in various functions of cell physiology, such as cell cycle control. [source]

The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors

CANCER SCIENCE, Issue 12 2003
Keigo Nishida
The Grb2-associated binder (Gab) family adapter proteins are scaffolding adapter molecules that display sequence similarity with Drosophila DOS (daughter of sevenless), which is a substrate for the protein tyrosine phosphatase Corkscrew. Gab proteins contain a pleckstrin homology (PH) domain and binding sites for SH2 and SH3 domains. A number of studies in multiple systems have implicated Gab in signaling via many different types of receptors, such as growth factor, cytokine, and antigen receptors, and via oncoproteins. Recent studies of Gab1 and Gab2 knockout mice have clearly indicated an important role for Gabs in vivo. Gab1-deficient mice die as embryos with multiple defects in placental, heart, skin, and muscle development. Gab2-deficient mice are viable, but have a defect in the mast cell lineages and in allergic reactions. Given the apparently central role played by Gab signaling via many receptors, delineating the precise mechanism(s) of Gab-mediated signaling is critical to understanding how cytokines, growth factors, and oncoproteins mediate a variety of biological activities: cell growth, differentiation, survival and malignant transformation. [source]