molecular mechanisms in signal transduction at the membrane

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molecular mechanisms in signal transduction at the membrane jay t groves1,2,3,4 and john kuriyan1,2,3,4 1departments of chemistry, university of california, berkeley, california, usa 2molecular and cell biology, university of california, berkeley, california, usa 3howard hughes medical institute, university of california, berkeley, california, usa 4physical biosciences division, lawrence berkeley national lab, berkeley, california, usa abstract signal transduction originates at the membrane, where the clustering of signaling proteins is a key step in transmitting a message. membranes are difficult to study, and their influence on signaling is still only understood at the most rudimentary level. recent advances in the biophysics of membranes, surveyed in this review, have highlighted a variety of phenomena that are likely to influence signaling activity, such as local composition heterogeneities and long-range mechanical effects. we discuss recent mechanistic insights into three signaling systems—ras activation, ephrin signaling and the control of actin nucleation—where the active role of membrane components …

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still hidden beneath the cloak. cell signaling relies on modular domains that generate protein-protein interactions at the membrane3,4. equally critical are domains that recognize specific phospholipids and are thereby responsive to changes in membrane composition5, as best exemplified by the family of protein kinase c (pkc) isozymes6,7. the pkc isozymes transduce signals arising from the hydrolysis of phospholipids in the membrane and have a protein kinase domain linked to c1 domains and a c2 domain (fig. 1). the c1 domains bind to diacylglycerol (dag), whereas the c2 domain binds to negatively charged lipids, such as phosphatidylinositol-4,5,- bisphosphate (pip2) and to ca2+ ions6,7. the activation of pkc involves priming by phosphorylation, followed by the recruitment of pkc to the membrane by pip2, ca2+ and dag7,8. one important principle that emerged from pkc studies is that the individual lipid- binding modules of pkc have insufficient affinity for their target lipids and so …

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tion? to address such questions, we have to directly view the signaling proteins in action on the membrane. this has posed a formidable challenge in the past, but the good news is that new strategies to image, synthesize and control membranes (in vitro, in vivo and through computational modeling) are coming of age. we believe that this is a particularly exciting frontier of current research, where major breakthroughs can be expected in the near future. to help spur the imagination, we review here a wide range of physical properties of membranes along with specific instances of their involvement in signal transduction. these range from relatively obvious effects, such as local concentration enhancement, to mechanisms for long-range cooperativity and emergent properties such as force sensing. more detailed discussion will focus on (i) activation of ras by the nucleotide exchange factor son of sevenless (sos), (ii) juxtacrine triggering of the ephrin type-a …

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indicators only. an excellent example of an emergent property resulting from protein binding to membrane surfaces is the self-organizing wave pattern of bacterial min proteins14 (fig. 2). these proteins are crucial for accurate cell division and undergo spatiotemporal oscillations in vivo. a simple mixture of mind, an atpase, and mine, a protein that stimulates the atpase activity of mind, has recently been observed to spontaneously organize into propagating wave patterns on supported membrane surfaces in vitro in the presence of atp. although the emergent behavior is complex, the system can be quantitatively understood in terms of a reaction-diffusion model for membrane-surface interactions14. importantly, the basic combination of properties that lead to this behavior is not so difficult to achieve, suggesting that dynamic spatial organization could be involved in a wide range of signaling processes. indeed, similar wave patterns of actin polymerization can be observed along the membranes of eukaryotic cells15. …

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l effect of the membrane and cytoskeleton on protein binding kinetics. importantly, antigen recognition by t cells is thought to depend largely on the details of tcr-pmhc binding kinetics. it is clear that the membrane is not a homogeneous fluid. it is a nanometer-scale emulsion of lipids, cholesterol and proteins in intimate association with the cortical cytoskeleton20. the concept of the membrane raft, a phase-separated domain or composition fluctuation, has been a topic of much debate in the context of cell-membrane organization. the debate has been exacerbated by attempts to oversimplify the complex but reasonably well-understood phenomena of miscibility and demixing in liquids. a comprehensive review clarifying some of these issues has recently been published21. cell membrane lipids and cholesterol show miscibility phase transitions and even critical- point phenomena at physiological temperatures. this has been observed in giant unilamellar vesicles (guvs) formed from synthetic or purified components22–24 as well as …

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О "molecular mechanisms in signal transduction at the membrane"

molecular mechanisms in signal transduction at the membrane jay t groves1,2,3,4 and john kuriyan1,2,3,4 1departments of chemistry, university of california, berkeley, california, usa 2molecular and cell biology, university of california, berkeley, california, usa 3howard hughes medical institute, university of california, berkeley, california, usa 4physical biosciences division, lawrence berkeley national lab, berkeley, california, usa abstract signal transduction originates at the membrane, where the clustering of signaling proteins is a key step in transmitting a message. membranes are difficult to study, and their influence on signaling is still only understood at the most rudimentary level. recent advances in the biophysics of membranes, surveyed in this review, have highlighted a vari...

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