Pub Date : 2003-01-01DOI: 10.1126/scisignal.1902003pe25
S. Foord
Heterodimerization enhances the complexity of ligand recognition and diversity of signaling responses of heterotrimeric guanine nucleotide-binding protein-coupled receptors (GPCRs). Many accessory proteins (for ion channels or GPCRs) appear to associate with their partners relatively early in the process whereby proteins are transported to the cell surface; their roles in modulating function may have evolved out of simple proximity to a protein that once upon a time they either facilitated or accompanied through the maturation process. The receptor activity-modifying proteins (RAMPs) are a family of single-transmembrane accessory proteins that heterodimerize with GPCRs and, thereby, allow individual GPCRs to recognize multiple ligands and to activate various signaling pathways in response to ligand binding. The M10 family of major histocompatibility complex (MHC) class 1b proteins has recently been shown to associate with murine vomeronasal V2R receptors, as well as to escort them to the cell surface. The exact role of M10 in modulating V2R function (or vice versa) remains to be determined.
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Pub Date : 2002-01-01DOI: 10.1126/stke.2002.128.re4
G. Bismuth, L. Boumsell
Semaphorins provide crucial attractive and repulsive cues involved in axon guidance. Several semaphorins have also been detected in cells of the immune system. Their influence on cell motility has been reported and is reminiscent of the biological function attributed to nervous system semaphorins. Receptors of the plexin and neuropilin family of proteins, also expressed by some immune cells, may be involved in semaphorin signaling in the immune system. However, semaphorins also affect the functioning of the immune system through receptors regulating lymphocyte activation. An important challenge in the future will be to determine whether, as in the nervous system, semaphorins help immune cells to establish connections with their appropriate targets.
{"title":"Controlling the immune system through semaphorins.","authors":"G. Bismuth, L. Boumsell","doi":"10.1126/stke.2002.128.re4","DOIUrl":"https://doi.org/10.1126/stke.2002.128.re4","url":null,"abstract":"Semaphorins provide crucial attractive and repulsive cues involved in axon guidance. Several semaphorins have also been detected in cells of the immune system. Their influence on cell motility has been reported and is reminiscent of the biological function attributed to nervous system semaphorins. Receptors of the plexin and neuropilin family of proteins, also expressed by some immune cells, may be involved in semaphorin signaling in the immune system. However, semaphorins also affect the functioning of the immune system through receptors regulating lymphocyte activation. An important challenge in the future will be to determine whether, as in the nervous system, semaphorins help immune cells to establish connections with their appropriate targets.","PeriodicalId":82678,"journal":{"name":"Science's STKE : signal transduction knowledge environment","volume":"26 1","pages":"re4"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82511200","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}
Pub Date : 2000-01-01DOI: 10.1126/scisignal.232000re1
J. Wrana
The transforming growth factor-beta (TGF-beta) superfamily of secreted polypeptide growth factors exerts extensive control over all aspects of development and homeostasis, and components of this pathway are often mutated in cancers and in several hereditary disorders. Apart from TGF-beta, the superfamily also includes the activins and the bone morphogenetic proteins. These factors signal through heteromeric complexes of type II and type I serine-threonine kinase receptors, which activate the downstream Smad signal transduction pathway. Three classes of Smads have been defined: the receptor-regulated Smads (R-Smads), the common-mediator Smads (co-Smads), and the antagonistic or inhibitory Smads (I-Smads). Receptor complexes activate the Smad pathway by interacting and phosphorylating specific R-Smads. Phosphorylation of the R-Smads causes dissociation from the receptor and induces assembly into complexes with Smad4, a co-Smad. This heteromeric complex then translocates into the nucleus, where the Smads function as transcriptional comodulators by recruiting coactivators or corepressors to Smad DNA binding partners. Thus, Smads transmit signals directly from the receptor kinase into the nucleus. Crosstalk between Smads and other signaling pathways occurs both in the cytosol and in the nucleus. In the cytosol, Smad translocation might be inhibited by mitogen-activated protein kinase-dependent phosphorylation, whereas in the nucleus Smads interact with a number of transcription factors that themselves are primary targets of other signaling pathways. Furthermore, Smad-dependent regulation of these targets often requires input from the primary signaling pathway. In these examples, Smad signaling may represent a secondary signal that modifies the output of the primary pathway. Consequently, the transcriptional response to TGF-beta family ligands may be dependent on what other signals are being received by the cell. Crosstalk may thus provide one explanation for the long-standing observation that the biological response to TGF-beta is often dependent on the extracellular environment of the cell.
{"title":"Crossing Smads.","authors":"J. Wrana","doi":"10.1126/scisignal.232000re1","DOIUrl":"https://doi.org/10.1126/scisignal.232000re1","url":null,"abstract":"The transforming growth factor-beta (TGF-beta) superfamily of secreted polypeptide growth factors exerts extensive control over all aspects of development and homeostasis, and components of this pathway are often mutated in cancers and in several hereditary disorders. Apart from TGF-beta, the superfamily also includes the activins and the bone morphogenetic proteins. These factors signal through heteromeric complexes of type II and type I serine-threonine kinase receptors, which activate the downstream Smad signal transduction pathway. Three classes of Smads have been defined: the receptor-regulated Smads (R-Smads), the common-mediator Smads (co-Smads), and the antagonistic or inhibitory Smads (I-Smads). Receptor complexes activate the Smad pathway by interacting and phosphorylating specific R-Smads. Phosphorylation of the R-Smads causes dissociation from the receptor and induces assembly into complexes with Smad4, a co-Smad. This heteromeric complex then translocates into the nucleus, where the Smads function as transcriptional comodulators by recruiting coactivators or corepressors to Smad DNA binding partners. Thus, Smads transmit signals directly from the receptor kinase into the nucleus. Crosstalk between Smads and other signaling pathways occurs both in the cytosol and in the nucleus. In the cytosol, Smad translocation might be inhibited by mitogen-activated protein kinase-dependent phosphorylation, whereas in the nucleus Smads interact with a number of transcription factors that themselves are primary targets of other signaling pathways. Furthermore, Smad-dependent regulation of these targets often requires input from the primary signaling pathway. In these examples, Smad signaling may represent a secondary signal that modifies the output of the primary pathway. Consequently, the transcriptional response to TGF-beta family ligands may be dependent on what other signals are being received by the cell. Crosstalk may thus provide one explanation for the long-standing observation that the biological response to TGF-beta is often dependent on the extracellular environment of the cell.","PeriodicalId":82678,"journal":{"name":"Science's STKE : signal transduction knowledge environment","volume":"18 1","pages":"re1"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75018155","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}
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