Molecular Organization and Signal Transduction at Intermembrane Junctions

Groves, Jay T.

doi:10.1002/anie.200461014

Cited by 27 publications

(30 citation statements)

References 140 publications

(143 reference statements)

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“…This review focuses on the application of synthetic multivalent ligands to the analysis of signaling complexes. [9,84] Experiments with multivalent ligands can address the next generation of questions concerning the function of receptors and signaling systems.…”

Section: Challenges To Studying Receptor Functionmentioning

confidence: 99%

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Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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Cell surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Evidence from biochemical and structural studies indicates that many receptors do not operate as individual entities, but rather as part of higher-order complexes (e.g. dimers and oligomers). Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Despite the proposed importance of receptor-receptor processes in cellular signaling, questions concerning the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication remain unanswered.Chemical synthesis can provide a variety of compounds with which to address the role of receptor assembly in signal transduction. The focus of this review is one such approach -the use of synthetic multivalent ligands to characterize receptor function. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. Their unique architectures imbue multivalent ligands with the ability to access binding modes not available to monovalent compounds. Multivalent ligands, therefore, are capable of illuminating aspects of inter-receptor processes that are not readily probed using conventional approaches. We suggest that, as focus shifts from investigations of the function of individual proteins and toward the analysis of multi-receptor signaling complexes, multivalent ligands will become even more valuable tools with which to ask sophisticated mechanistic questions. Further, multivalent ligands may provide new opportunities for manipulating receptor systems for the deconvolution of pathways, diagnosis, and, ultimately, the treatment of disease.

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Section: Challenges To Studying Receptor Functionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9] Cell surface receptors do not typically operate as individual entities; rather, they function in concert. An ermerging paradigm is that receptors within multi-receptor signaling complexes communicate with each other.…”

Section: Introduction To Receptor Functionmentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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“…Bei einem wichtigen Mechanismus für eine effiziente Signalauslösung werden die Funktionen mehrerer Zelloberflä-chenrezeptoren gekoppelt; [1][2][3][4][5][6][7][8][9] diese Rezeptoren reagieren meist nicht als individuelle Komponenten sondern konzertiert. Dabei verfestigt sich die Auffassung, dass die Rezeptoren innerhalb eines Multirezeptor-Komplexes miteinander kommunizieren.…”

Section: Einführung -Die Funktion Von Rezeptorenunclassified

“…[9,129,[216][217][218] In einer Untersuchung befasste man sich mit dem Mechanismus, nach dem die T-Zell-Reaktionen durch den Corezeptor CD28 verstärkt werden. [87] .…”

Section: T-zell-rezeptorenunclassified

Synthetische multivalente Liganden als Sonden für die Signaltransduktion

2006

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Zelloberflächenrezeptoren nehmen Informationen aus der extrazellulären Umgebung auf und stimmen die intrazellulären Reaktionen darauf ab. Viele dieser Rezeptoren agieren nicht einzeln, sondern als Teil von dimeren oder oligomeren Komplexen. Die funktionelle Kopplung mehrerer Rezeptoren verleiht den Signaltransduktionswegen möglicherweise die Empfindlichkeit, die für die Regulation zellulärer Reaktionen erforderlich ist. Außerdem können Multirezeptor‐Signalkomplexe ansonsten überlappende Signalkaskaden räumlich trennen. Die Mechanismen, das Ausmaß und die Konsequenzen der Colokalisation und die Kommunikation zwischen den Rezeptoren sind noch unklar, doch synthetische Verbindungen können dabei helfen, die Rolle der Rezeptorassoziationen bei der Signaltransduktion zu ermitteln. Solche multivalenten Liganden können Bindestellen verschiedener Größe, Form, Valenz, Orientierung und räumlicher Anordnung enthalten. Der Schwerpunkt dieses Aufsatzes liegt auf dem Einsatz synthetischer multivalenter Liganden, um die Rezeptorfunktion zu charakterisieren.

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“…Herein we report a ligand-modified fluid supported-lipid bilayer (SLB) [5,10,[18][19][20][21][22] assay system that can be used to functionally display soluble ligands to cells in situ (Figure 1 A). By displaying soluble ligands on a SLB surface, both solution behavior (the ability to become locally enriched by reaction-diffusion processes) and solid behavior (the ability to control the spatial location of the ligands in an open system) could be combined.…”

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confidence: 99%