{"title":"Clustering of membrane proteins in the pre-stimulation stage is required for signal transduction: a computer analysis","authors":"Hiroshi Kobayashi, R. Azuma, A. Konagaya","doi":"10.1002/SITA.200790020","DOIUrl":"https://doi.org/10.1002/SITA.200790020","url":null,"abstract":"The physiological significance of membrane protein clustering for signal transduction was examined theoretically using a Monte Carlo computer simulation. Simulation results revealed that pre-stimulation clustering of membrane proteins enhanced signal transduction. Membrane protein clustering induced by the binding of external stimuli provided no kinetic advantage in terms of formation rate or maximum quantity of active membrane receptor complexes. These data suggested that membrane proteins associate weakly in the clustering areas of non-stimulated cells, and that their association is strengthened upon binding of extracellular stimuli to the membrane receptor. Additionally, the number of cytosolic proteins recruited to membrane receptor complexes was not increased by the membrane complex clustering, except when cytosolic signal proteins were localized to a narrow area such as a tunnel that ran from the membrane cluster to the nucleus. Simulations were carried out on a conventional personal computer under Windows XP or 2000 operating systems. Since neither special computing hardware nor special training is required, our simulation procedure could be easily adapted for kinetic analysis of any signal transduction pathway.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"110 1","pages":"329-339"},"PeriodicalIF":0.0,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200790020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The stoichiometry of the T cell antigen receptor and its implications for the signal transduction mechanism","authors":"W. Schamel","doi":"10.1002/SITA.200600123","DOIUrl":"https://doi.org/10.1002/SITA.200600123","url":null,"abstract":"The T cell antigen receptor (TCR·CD3) is a multi-subunit complex mediating T cell development and activation. The molecular mechanism of how this receptor transmits information across the membrane is still an enigma. The stoichiometry and architecture of this receptor in the membrane are under intense investigation, since they are important in deciphering the signal transduction mechanism of the TCR·CD3. This review highlights the evidence that TCR·CD3 is found on unstimulated T cells in monovalent (one ligand-binding site per receptor) as well as in multivalent forms. Distinct detergents affect the integrity of the multivalent receptor differently, explaining controversial findings of TCR·CD3 stoichiometries as determined by biochemical means. The existence of multivalent receptors is not compatible with current models of TCR·CD3 triggering. Therefore, I discuss the novel “permissive geometry model” that combines multivalent TCR·CD3s, the requirement for multimeric ligands for receptor triggering and conformational changes at CD3.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"56 1","pages":"311-319"},"PeriodicalIF":0.0,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harald Bradl, Christian Vettermann, W. Schuh, S. Meister, H. Jäck
{"title":"The pre‐B cell receptor and its ligands – it takes two to tango","authors":"Harald Bradl, Christian Vettermann, W. Schuh, S. Meister, H. Jäck","doi":"10.1002/SITA.200500055","DOIUrl":"https://doi.org/10.1002/SITA.200500055","url":null,"abstract":"DFG Training Program GK592, Nikolaus Fiebiger Center for Molecular Medicine, University ofErlangen and Nurnberg, GermanyThe development of early precursor B cells is governed by the surface-bound pre-B cell receptorconsisting of the immunoglobulin µ heavy chain, the surrogate light chain components λ5andVpreB, and the signal transducing subunits immunglobulin α/immunglobulin β. The pre-B cell re-ceptor controls clonal expansion, survival and efficient differentiation of functional B lymphoid pre-cursors; however, it is still controversial how signals from this receptor are initiated. Recent studieswith Abelson murine leukemia virus (Abl-MuLV)-transformed pre-B cell lines suggest that the N-terminal non-immunoglobulin portion of λ5, the so-called unique tail, is required to initiate cell-autonomous signals by mediating self-aggregation of the pre-B cell receptor (pre-BCR). Strikinglyhowever, the λ5 unique tail also controls the interaction with two different groups of stroma cell-derived pre-BCR ligands, namely heparan sulfate glycosaminoglycans and surface-associated ga-lectin-1. Even though these findings are not mutually exclusive, they refresh the discussion aboutpotential modes of pre-BCR signal initiation. In this review, we discuss recent key findings andpropose an integrative model for ligand dependent and independent initiation of pre-BCR signalsduring selection of functional B cell precursors.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"7 1","pages":"299-310"},"PeriodicalIF":0.0,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Signal transduction in vestibular adaptation to microgravity – A still unsolved problem","authors":"E. Horn","doi":"10.1002/SITA.200600107","DOIUrl":"https://doi.org/10.1002/SITA.200600107","url":null,"abstract":"In men and monkeys as well as adult and developing fish (Fundulus heteroclictus, Opsanus tau, Xiphophorus helleri), amphibian (Rana catesbeiana, Xenopus laevis) and rodents, microgravity cause significant behavioral, physiological and psychophysical sensitivity changes within the vestibular system. Some of these observations point to sensitization of the vestibular system during exposure to weightlessness. The review presents mechanisms that might contribute to vestibular sensitization during microgravity adaptation. They include (1) stimulus transduction within vestibular hair cells, (2) activation of immediate early genes within central afferent and efferent vestibular nuclei, and (3) modifications of cellular transcription factors' activity during early development.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"21 2","pages":"240-247"},"PeriodicalIF":0.0,"publicationDate":"2007-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dlk/ZIP kinase, a novel Ser/Thr‐specific protein kinase with multiple functions","authors":"K. Scheidtmann","doi":"10.1002/SITA.200600112","DOIUrl":"https://doi.org/10.1002/SITA.200600112","url":null,"abstract":"Dlk/ZIP kinase is a member of the DAP kinase family which has been implicated in apoptosis. However, Dlk/ZIP kinase does not induce apoptosis per se. Rather, downregulation of Dlk/ZIP kinase by siRNA results in apoptosis and multinucleated cells suggesting that Dlk/ZIP kinase fulfills a vital function in processes other than apoptosis. Indeed, Dlk/ZIP kinase interacts with several transcription and splicing factors pointing to a role in transcription, presumably via chromatin modification. Moreover, it appears to participate in regulation of cell polarity and contractile processes in non-muscle or smooth muscle cells. Finally, Dlk/ZIP kinase seems to play a role in mitosis, particularly cytokinesis. Thus, rather than being a proapoptotic kinase, Dlk/ZIP kinase participates in diverse and vital processes.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"33 20","pages":"248-259"},"PeriodicalIF":0.0,"publicationDate":"2007-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Sobocki, I. Ray, P. Cano‐Sánchez, Probal Banerjee, E. Azmitia
{"title":"Serotonin 1A receptor coupling to NF‐κB studied using inducible receptor expression in hippocampal neuron‐derived cells","authors":"T. Sobocki, I. Ray, P. Cano‐Sánchez, Probal Banerjee, E. Azmitia","doi":"10.1002/SITA.200600087","DOIUrl":"https://doi.org/10.1002/SITA.200600087","url":null,"abstract":"The mechanism of serotonin 1A receptor (5-HT1A-R) mediated activation of NF-κB has been studied in non-neural cells, but this pathway has not been elucidated in neuronal cells. We have used inducible expression of the 5-HT1A-R in the hippocampal neuron-derived HN2 cells to analyze the coupling of this receptor to NF-κB. A construct harboring luciferase cDNA driven by a minimal promoter under the control of an NF-κB-specific enhancer element was transfected into these 5-HT1A-R-expressing HN2 cells. Using luciferase expression in the transfected cells, we have studied 5-HT1A-R agonist evoked activation of NF-κB. Inhibition of either mitogen activated protein kinase (MAPK) pathway with PD98059 or protein kinase C (PKC) with GFX caused elevation of the basal level of NF-κB activity but did not affect 5-HT1A-R mediated activation of NF-κB. Furthermore, neither the basal level of NF-κB nor its activation by a 5-HT1A-R agonist was altered by dibutyrylcAMP. Thus, the MAPK pathway and PKC cause inhibition of the basal NF-κB activity and the 5-HT1A-R-linked NF-κB activation does not require MAPK, PKC, and cAMP. Intriguingly, Western blot analysis showed that 5-HT1A-R mediates activation of both CaMKII and PI-3K. This 5-HT1A-R-evoked the stimulation of CaMKII was reversed in the presence of a PI-3K inhibitor. Therefore, the likely mechanism of 5-HT1A-R mediated induction of NF-κB in neuronal cells involves activation of PI-3K upstream of CaMKII. This reveals a novel pathway that could be crucial in the functional activity of brain neurons.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"67 2","pages":"260-269"},"PeriodicalIF":0.0,"publicationDate":"2007-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"p90 Ribosomal S6 kinases‐ eclectic members of the human kinome","authors":"Kwok Y. Lee, P. Bignone, T. Ganesan","doi":"10.1002/SITA.200600091","DOIUrl":"https://doi.org/10.1002/SITA.200600091","url":null,"abstract":"The p90 ribosomal S6 kinase (RPS6KA1-6; RSK1-6) family represents an important family of conserved serine-threonine kinases among the higher eukaryotes. RSKs are identified by the presence of two non-identical and active kinase domains that is unique amongst the kinome. These kinases are involved in a multitude of essential processes in the cell, ranging from apoptosis and transcriptional regulation and activation of immediate early genes to the maintenance of the cell cycle and growth. They are also important in the regulation of the cell cycle in G2, meiosis I and II. The mutation and loss of catalytic activity of RSK2 causes Coffin-Lowry syndrome. This review provides a concise and focused perspective on the current understanding of the function of RSKs and their substrates.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"90 1","pages":"225-239"},"PeriodicalIF":0.0,"publicationDate":"2007-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Strell, F. Entschladen, P. Bastian, B. Niggemann, K. Zänker, K. Lang
{"title":"The generation of locomotory forces in the spontaneous and norepinephrine‐induced migration of carcinoma cells","authors":"C. Strell, F. Entschladen, P. Bastian, B. Niggemann, K. Zänker, K. Lang","doi":"10.1002/SITA.200600088","DOIUrl":"https://doi.org/10.1002/SITA.200600088","url":null,"abstract":"The migration of tumor cells is essential for metastasis development. We distinguish two types of migration with regard to the dynamics and molecular basis: a slow, spontaneous type of migration is induced by the extracellular matrix. This type of migration is myosin II-independent. A fast type of migration is induced by ligands to G protein-coupled receptors, of which norepinephrine is the most potent. This migration depends on the myosin II activity. However, there is still discordance to which part other cytoskeletal components such as actin, myosin and tubulin contribute to these two types of tumor cell migration. Here we present a study on the role of several cytoskeletal proteins in the spontaneous and induced migration of breast and colon carcinoma cells by time-lapse videomicroscopy. The actin reorganization is essential for each type of cell migration. We have shown previously the important function of myosin II for the norepinephrine-induced migration, whereas we show herein that myosin VI is not involved. Most interestingly, stabilization of the microtubules reduced both types of migration, whereas a disruption increased the spontaneous and inhibited the norepinephrine-induced migration. These data suggest that the force generation is different in the spontaneous and the induced migration of carcinoma cells.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"6 2","pages":"270-278"},"PeriodicalIF":0.0,"publicationDate":"2007-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Beltrán, B. Galindo, E. Rodríguez‐Miranda, Daniel Sánchez
{"title":"Signal transduction mechanisms regulating ion fluxes in the sea urchin sperm","authors":"C. Beltrán, B. Galindo, E. Rodríguez‐Miranda, Daniel Sánchez","doi":"10.1002/SITA.200600129","DOIUrl":"https://doi.org/10.1002/SITA.200600129","url":null,"abstract":"Ion permeability changes involving ion channels and transporters are essential for fertilization, since they are key elements in sperm-egg signaling and environmental sensing. Changes modulated by external factors and components from the outer layer of the homologous egg, like the sperm-activating peptides and the fucose-sulfate glycoconjugate, trigger complex signaling systems in the sperm that modulate how sperm swim, find the egg and fertilize it. These signaling systems depend on plasma membrane ion permeability and involve an alteration of second messenger levels, changes of membrane potential and intracellular Ca2+, Na+ and pH, along with changes in sperm morphology in the case of the acrosome reaction (AR). New procedures to elucidate the signaling pathways implicated in sperm ion transport have expanded the opportunities to dissect sperm-egg signaling revealing how sperm ion channels participate in activation, motility, chemotaxis, and the AR. The sperm signaling pathways involve a large variety of ion channels and transporters, which are discretely localized and finely orchestrated to play specific roles that define the elaborate performance of sperm and allow a successful fertilization. In this review we will focus on the signaling molecules involved in the final aim of the sperm, to reach and fertilize the egg.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"37 7","pages":"103-117"},"PeriodicalIF":0.0,"publicationDate":"2007-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Secondary axis specification in sea urchin embryos","authors":"C. Bradham, D. McClay","doi":"10.1002/SITA.200600121","DOIUrl":"https://doi.org/10.1002/SITA.200600121","url":null,"abstract":"Secondary axis specification is a process that relies on asymmetric nuclearization of transcription factors in flies and vertebrates, such that the crucial factor is nuclear and therefore functional only in cells along one side of the embryo. In vertebrates, this transcription factor is β-catenin, which is canonically activated downstream from Wnt signals. However, the sea urchin uses asymmetric β-catenin nuclearization during specification of the primary animal-vegetal axis, rather than the secondary oral-aboral (OA) axis. OA specification relies instead on the asymmetric localization of p38 MAPK, a signaling kinase that directly modulates transcription factor activity. A number of genes are expressed in the oral territory downstream from p38, including Nodal and Goosecoid, both of which are associated with secondary axis specification in vertebrate embryos. Because the p38 asymmetry is the earliest known event in the specification of the OA axis, an outstanding question concerns identifying the apparatus upstream from p38 that regulates its asymmetrical activity. Intriguingly, this may be controlled by reactive oxygen species released from the mitochondria, which are asymmetrically distributed about the OA axis.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"22 3","pages":"181-186"},"PeriodicalIF":0.0,"publicationDate":"2007-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}