Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine diphosphate-ribosylation factor (Arf) proteins are members of the Arf arm of the Ras superfamily of guanosine triphosphate (GTP)-binding proteins. Arfs are named for their activity as cofactors for cholera toxin-catalyzed adenosine diphosphate-ribosylation of the heterotrimeric G protein Gs. Physiologically, Arfs regulate membrane traffic and the actin cytoskeleton. Arfs function both constitutively within the secretory pathway and as targets of signal transduction in the cell periphery. In each case, the controlled binding and hydrolysis of GTP is critical to Arf function. The activities of some guanine nucleotide exchange factors (GEFs) and guanosine triphosphatase (GTPase)-activating proteins (GAPs) are stimulated by phosphoinositides, including phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA), likely providing both a means to respond to regulatory signals and a mechanism to coordinate GTP binding and hydrolysis. Arfs affect membrane traffic in part by recruiting coat proteins, including COPI and clathrin adaptor complexes, to membranes. However, Arf function likely involves many additional biochemical activities. Arf activates phospholipase D and phosphatidylinositol 4-phosphate 5-kinase with the consequent production of PA and PIP2, respectively. In addition to mediating Arf's effects on membrane traffic and the actin cytoskeleton, PA and PIP2 are involved in the regulation of Arf. Arf also works with Rho family proteins to affect the actin cytoskeleton. Several Arf-binding proteins suspected to be effectors have been identified in two-hybrid screens. Arf-dependent biochemical activities, actin cytoskeleton changes, and membrane trafficking may be integrally related. Understanding Arf's role in complex cellular functions such as protein secretion or cell movement will involve a description of the temporal and spatial coordination of these multiple Arf-dependent events.
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PMID:Molecular aspects of the cellular activities of ADP-ribosylation factors. 1175 22

The activation of the small guanosine triphosphatase Ras is critical for many biological events. It is therefore not surprising that the ubiquitously expressed Ras guanine nucleotide exchange factor (GEF) SOS (Son of Sevenless), which couples protein tyrosine kinases to Ras activation, is under tight autoinhibitory control. Several studies have revealed how multiple regulatory domains might affect SOS activity. Most notably, a second Ras-binding site on SOS allosterically regulates the duration and amplitude of Ras activation. This allosteric Ras-GTP is produced by another GEF, Ras guanine nucleotide-releasing protein 1 (RasGRP1). SOS and RasGRP1 are both activated downstream of phospholipase D(2), and gain-of-function mutants of SOS contribute to inherited diseases. These studies not only enable us to better appreciate the complexity of the regulation of GEFs but also prompt us to reevaluate our current understanding of pathways that lead to Ras activation.
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PMID:New insights into the mechanisms of SOS activation. 1804 41

The two mammalian phosphatidylcholine (PC)-selective phospholipase D (PLD) enzymes remove the choline head group from PC to produce phosphatidic acid (PA). PA stimulates phosphatidylinositol(4)phosphate 5-kinases, can function as a binding site for membrane proteins, is required for certain membrane fusion or fission events and is an important precursor for the production of diacylglycerol (DAG). Both PA and DAG are lipids that favor negatively curved membranes rather than planar bilayers and can reduce the energetic barrier to membrane fission and fusion. Recent data provide a mechanistic explanation for the role PLDs play in some aspects of membrane traffic and provide an explanation for why some membrane fusion reactions require PA and some do not. PLDs also act as guanosine triphosphatase-activating proteins for dynamin and may participate with dynamin in the process of vesicle fission.
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PMID:Molecular mechanisms of PLD function in membrane traffic. 1842 60

During chemotaxis, activation of the small guanosine triphosphatase Rac is spatially regulated to organize the extension of membrane protrusions in the direction of migration. In neutrophils, Rac activation is primarily mediated by DOCK2, an atypical guanine nucleotide exchange factor. Upon stimulation, we found that DOCK2 rapidly translocated to the plasma membrane in a phosphatidylinositol 3,4,5-trisphosphate-dependent manner. However, subsequent accumulation of DOCK2 at the leading edge required phospholipase D-mediated synthesis of phosphatidic acid, which stabilized DOCK2 there by means of interaction with a polybasic amino acid cluster, resulting in increased local actin polymerization. When this interaction was blocked, neutrophils failed to form leading edges properly and exhibited defects in chemotaxis. Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis.
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PMID:Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. 1937 20

Cell division and expansion require the ordered arrangement of microtubules, which are subject to spatial and temporal modifications by developmental and environmental factors. Understanding how signals translate to changes in cortical microtubule organization is of fundamental importance. A defining feature of the cortical microtubule array is its association with the plasma membrane; modules of the plasma membrane are thought to play important roles in the mediation of microtubule organization. In this review, we highlight advances in research on the regulation of cortical microtubule organization by membrane-associated and membrane-tethered proteins and lipids in response to phytohormones and stress. The transmembrane kinase receptor Rho-like guanosine triphosphatase, phospholipase D, phosphatidic acid, and phosphoinositides are discussed with a focus on their roles in microtubule organization.
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PMID:Regulation of developmental and environmental signaling by interaction between microtubules and membranes in plant cells. 2668 89