Adaptor Molecule (adaptor + molecule)

Distribution by Scientific Domains


Selected Abstracts


MyD88 expression in the rat dental follicle: implications for osteoclastogenesis and tooth eruption

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2010
Dawen Liu
Liu D, Yao S, Wise GE. MyD88 expression in the rat dental follicle: implications for osteoclastogenesis and tooth eruption. Eur J Oral Sci 2010; 118: 333,341. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Myeloid differentiation factor 88 (MyD88) is a key adaptor molecule in the interleukin (IL)-1 and IL-18 toll-like receptor signaling pathways. Because MyD88 is present in dental follicle (DF) cells in vitro, the purpose of this study was to determine its chronological expression in vivo, as well as its possible role in osteoclastogenesis and tooth eruption. An oligo DNA microarray was used to determine expression of the Myd88 gene in vivo in the DFs from the first mandibular molars of postnatal rats from days 1 to 11. The results showed that MyD88 was expressed maximally on day 3. Using small interfering RNA (siRNA) to knock down MyD88 expression in the DF cells also reduced the expression of the nuclear factor-kappa B-1 (NFKB1) and monocyte chemoattractant protein 1 (MCP-1) genes. Interleukin-1, up-regulated the expression of NFKB1, MCP-1, and receptor activator of nuclear factor kappa B ligand (RANKL), but knockdown of MyD88 nullified this IL-1, effect. Conditioned medium from DF cells with MyD88 knocked down had reduced chemotactic activity for mononuclear cells and reduced osteoclastogenesis, as opposed to controls. In conclusion, the maximal expression of MyD88 in the DF of postnatal day 3 rats may contribute to the major burst of osteoclastogenesis needed for eruption by up-regulating MCP-1 and RANKL expression. [source]


The adaptor molecule FADD from Xenopus laevis demonstrates evolutionary conservation of its pro-apoptotic activity

GENES TO CELLS, Issue 12 2004
Kazuhiro Sakamaki
FADD is an adaptor protein that transmits apoptotic signals from death receptors such as Fas to downstream initiator caspases in mammals. We have identified and characterized the Xenopus orthologue of mammalian FADD (xFADD). xFADD contains both a death effector domain (DED) and a death domain (DD) that are structurally homologous to those of mammalian FADD. We observed xFADD binding to Xenopus caspase-8 and caspase-10 as well as to human caspase-8 and Fas through interactions with their homophilic DED and DD domains. When over-expressed, xFADD was also able to induce apoptosis in wild-type mouse embryonic fibroblasts (MEF), but not in caspase-8-deficient MEF cells. In contrast, DED-deficient xFADD (xFADDdn) acted as a dominant-negative mutant and prevented Fas-mediated apoptosis in mammalian cell lines. These results indicate that xFADD transmits apoptotic signals from Fas to caspase-8. Furthermore, we found that transgenic animals expressing xFADD in the developing heart or eye under the control of tissue-specific promoters show abnormal phenotypes. Taken together, these results suggest that xFADD can substitute functionally for its mammalian homologue in death receptor-mediated apoptosis, and we suggest that xFADD functions as a pro-apoptotic adaptor molecule in frogs. Thus, the structural and functional similarities between xFADD and mammalian FADD provide evidence that the apoptotic pathways are evolutionally conserved across vertebrate species. [source]


Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and V,14 NKT cells

IMMUNOLOGY, Issue 1pt2 2009
Hiroshi Furukawa
Summary Concanavalin A (Con A)-induced hepatitis is a T-cell-mediated murine experimental model of autoimmune hepatitis. Mice lacking V,14 NKT cells were found to be less sensitive to this hepatitis and the MRL/Mp- Faslpr/lpr (MRL/lpr; i.e. Fas deficient) mice were also less sensitive. We report herein that MRL/Mp- Faslpr/lpr - Saprpl/, (MRL/lpr/rpl) mice lack V,14 NKT cells and are deficient in the Fas antigen but sensitive to Con A-induced hepatitis. The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. We previously reported new mutant mice found among MRL/lpr mice and revealed that SAP deficiency led to the regression of autoimmune phenotypes in mutant MRL/lpr/rpl mice. It was also revealed that CD4+ and CD8+ T cells were effector cells and that blockade of 2B4, one of the SLAM family receptors, inhibited the induction of hepatitis in MRL/lpr/rpl mice. These data suggest that signals mediated by molecules other than SAP from 2B4 in T cells played important roles in the induction of hepatitis in MRL/lpr/rpl mice. [source]


New concepts regarding focal adhesion kinase promotion of cell migration and proliferation

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006
Braden D. Cox
Abstract Focal adhesion kinase (FAK) is a non-receptor cytoplasmic tyrosine kinase that plays a key role in the regulation of proliferation and migration of normal and tumor cells. FAK associates with integrin receptors and recruits other molecules to the site of this interaction thus forming a signaling complex that transmits signals from the extracellular matrix to the cell cytoskeleton. Crk-associated substrate (CAS) family members appear to play a pivotal role in FAK regulation of cell migration. Cellular Src bound to FAK phosphorylates CAS proteins leading to the recruitment of a Crk family adaptor molecule and activation of a small GTPase and c-Jun N-terminal kinase (JNK) promoting membrane protrusion and cell migration. The relocalization of CAS and signaling through specific CAS family members appears to determine the outcome of this pathway. FAK also plays an important role in regulating cell cycle progression through transcriptional control of the cyclin D1 promoter by the Ets B and Kruppel-like factor 8 (KLF8) transcription factors. FAK regulation of cell cycle progression in tumor cells requires Erk activity, cyclin D1 transcription, and the cyclin-dependent kinase (cdk) inhibitor p27Kip1. The ability of FAK to integrate integrin and growth factor signals resulting in synergistic promotion of cell migration and proliferation, and its potential regulation by nuclear factor kappa B (NF,B) and p53 and a ubiquitously expressed inhibitory protein, suggest that it is remarkable in its capacity to integrate multiple extracellular and intracellular stimuli. J. Cell. Biochem. © 2006 Wiley-Liss, Inc. [source]


The cell migration protein Grb7 associates with transcriptional regulator FHL2 in a Grb7 phosphorylation-dependent manner

JOURNAL OF MOLECULAR RECOGNITION, Issue 1 2009
Sharareh Siamakpour-Reihani
Abstract Grb7 is an adaptor molecule that can mediate signal transduction from multiple cell surface receptors to various downstream signaling pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase (RTK), erbB2, are overexpressed in 20,30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, though the participants in these pathways have not been determined. In this study, we report that Grb7 interacts with four and half lim domains isoform 2 (FHL2), a transcription regulator with an important role in oncogenesis, including breast cancer. Additionally, in yeast 2-hybrid (Y2H) assays, we show that the interaction is specific to the Grb7 RA and PH domains. We have also demonstrated that full-length (FL) Grb7 and FHL2 interact in mammalian cells and that Grb7 must be tyrosine phosphorylated for this interaction to occur. Immunofluorescent microscopy demonstrates possible co-localization of Grb7 and FHL2. A model with supporting NMR evidence of Grb7 autoinhibition is proposed. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Differential expression of lysosomal associated membrane protein (LAMP-1) during mammalian spermiogenesis

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2003
Ricardo D. Moreno
Abstract The mammalian acrosome is a secretory vesicle of mature sperms that plays an important role in fertilization. Recent evidence had pointed out that some components found at endosomes in somatic cells are associated with the developing acrosome during the early steps of spermiogenesis. Moreover, the mammalian acrosome contains many enzymes found within lysosomes in somatic cells. In this work, we studied the dynamics of some components of the endosome/lysosome system, as a way to understand the complex membrane trafficking circuit established during spermatogenesis. We show that the cation independent-mannose-6-phosphate receptor (CI-MPR) is transiently expressed in the cytoplasm of mid-stage spermatids (steps 5,11). On the other hand, ,-adaptin, an adaptor molecule of a complex involved in trafficking from the Golgi to lysosomes, was expressed in cytoplasmic vesicles only in pachytene and Cap-phase spermatids (steps 1,5). Our major finding is that the lysosomal protein LAMP-1 is differentially expressed during spermiogenesis. LAMP-1 appears late in spermatogenesis (Acrosome-phase) contrasting with LAMP-2, which is present throughout the complete process. Both proteins appear to be associated with cytoplasmic vesicles and not with the developing acrosome. None of the studied proteins is present in epididymal spermatozoa. Our results suggest that the CI-MPR could be involved in membrane trafficking and/or acrosomal shaping during spermiogenesis. Mol. Reprod. Dev. 66: 202,209, 2003. © 2003 Wiley-Liss, Inc. [source]


Epidermal growth factor-dependent enhancement of axonal regeneration in the pond snail Lymnaea stagnalis: Role of phagocyte survival

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2005
Petra M. Hermann
Abstract Peripheral nerve injury triggers complex responses from neuronal as well as from multiple nonneuronal cell types. These responses are coordinated by a wide spectrum of secreted and nonsecreted factors, including growth factors, cytokines, and cell adhesion molecules. These molecules originate from different sources and act both locally at the site of injury as well as centrally at the location of the neuronal cell bodies. One of the signal systems frequently implicated in this process is the epidermal growth factor (EGF) family and its receptors. Expression of members of this family as well as that of EGF-receptors is upregulated in different cell types after peripheral nerve injury. However, the functional significance of this response is unclear. Using a simple invertebrate model system (Lymnaea stagnalis), the present study implicates the EGF/EGF-receptor system in the survival of ionized calcium-binding adaptor molecule 1 (Iba1)-positive phagocytes that reside in the nervous system. We show that inhibiting the EGF-signaling pathway enhances cell death in this type of cell, an effect paralleled by a substantial reduction in axonal regeneration. Therefore, complementing our previous observation that Lymnaea EGF provides trophic support to axotomized neurons, the present results emphasize the significance of nonneuronal actions of EGF receptor ligands in axonal regeneration. Thus, we add a novel perspective to the ongoing discussion on the functional significance of the EGF signaling system in the injury responses of the nervous system. J. Comp. Neurol. 492:383,400, 2005. © 2005 Wiley-Liss, Inc. [source]


Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors

JOURNAL OF INTERNAL MEDICINE, Issue 6 2007
B. Albiger
Abstract. The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs. [source]


Serine/threonine kinase PKR: A sentinel kinase that discriminates a signaling pathway mediated by TLR4 from those mediated by TLR3 and TLR9

AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2007
Yusuke Asakura
Abstract Cells of the innate immune system discriminate between "noninfectious self" and "infectious nonself" via pattern recognition receptors known as Toll-like receptors (TLRs). Though TLRs and the related interleukin 1 receptors share considerable homology in their cytoplasmic domains and adaptor molecules, signaling cascades may substantially differ from one another depending on the adaptor proteins recruited. Here we show that ectopic overexpression of catalytically inactive dominant-negative PKR expression system suppressed NF- , B activation mediated by TLR3, TLR9, TNF receptor 1 and 2 (TNF-R 1/2), but not by TLR4. Physiological relevance of the observations described here are discussed. Am. J. Hematol 2007. © 2006 Wiley-Liss, Inc. [source]