ARF and PITP restore GTPγS-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis

Fensome, Amanda; Cunningham, Emer; Prosser, Simon; Tan, Siow Khoon; Swigart, Philip M.; Thomas, Geraint M. H.; Hsuan, J. Justin; Cockcroft, Shamshad

doi:10.1016/s0960-9822(09)00454-0

Cited by 164 publications

(141 citation statements)

References 40 publications

(94 reference statements)

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“…We postulate that PIPKH may play a similar role. ARF family members, in particular ARF-6, colocalize with type I PIPKs and are known to be activators of phospholipase D. A product of phospholipase D, phosphatidic acid, has been demonstrated to stimulate type I PIPKs, leading to the hypothesis that ARFs stimulate PIPKs indirectly, by increasing production of an allosteric effector molecule and not by any direct interaction (23). Type I PIPKs are highly active when expressed as bacterial GST fusion proteins and do not seem to require any cofactor for enhancement of activity when measured in a purified preparation.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Phosphoinositide Phosphate Kinase Homolog

Chang

Field

Rameh

et al. 2004

Journal of Biological Chemistry

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Three related phosphatidylinositol 4-phosphate 5-kinases (PI(4)P 5-kinases) have been identified in mammalian cells (types I␣, I␤, and I␥) and appear to play distinct roles in actin remodeling. Here we have identified a fourth member of this family by searching the human genome and EST data bases. This new protein, which we have designated phosphatidylinositol phosphate kinase homolog (PIPKH), is expressed at relatively high levels in brain and testis. Immunoprecipitates of PIPKH expressed in mammalian cells contain PI(4)P 5-kinase activity, but this activity is not affected by mutations in residues that inactivate other type I PI(4)P 5-kinases. We show that the PI(4)P 5-kinase activity in PIPKH immunoprecipitates can be explained by the ability of PIPKH to heterodimerize with other type I PI(4)P 5-kinases. Transfection of 293t cells with PIPKH resulted in >8-fold increase in total phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P 3 ) without a significant net increase in total PI(4,5)P 2 . When coexpressed with PIPKH, green fluorescent protein (GFP) fusion construct of the pleckstrin homology domain from Bruton's tyrosine kinase (GFP-BTK-PH) localized in intracellular vesicular structures, suggesting an unusual intracellular site of PI(3,4,5)P 3 production. Finally, expression of PIPKH induced the reorganization of actin from predominantly stress fibers to predominantly foci and comets similar to those observed previously in cells infected with the intracellular pathogen Listeria or transfected with recombinant PIPKI␣. These results suggest that PIPKH acts as a scaffold to localize and regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P 3 .Control of cellular functions involving membrane trafficking and adhesion requires rapid, reversible, and localized assembly of the actin cytoskeleton as well as of other functional complexes such as focal adhesions (1, 3-6). These assemblages of structural and signaling proteins provide a delimited zone of infrastructure, mechanical support, or directionality for dynamic membrane processes. Rapid and reversible assembly of the cytoskeletal framework for membrane vesicle formation, endoand exocytosis, and cell migration is regulated by the generation of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) 1 by phosphatidylinositol phosphate kinases (PIPKs) (5). It is now well established that this phosphoinositide is a signaling molecule in its own right, acting through several actin-binding proteins, members of the Wiscott-Aldrich Syndrome protein (WASP) family of proteins, and the Arp2/3 complex (7), as well as by controlling the localization of a subset of proteins containing pleckstrin homology (PH) domains. Dynamin, a large GTPase that is required for fission of nascent vesicles from Golgi and plasma membranes, binds to PI(4,5)P 2 by its PH domain and is found at actin-rich sites in peripheral ruffles of eukaryotic cells as well as in actin comets and tails generated by the intracellular pathogen Listeria or by overexpression of type I PIPKs (5,8,9). In ad...

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Phosphoinositide Phosphate Kinase Homolog

Chang

Field

Rameh

et al. 2004

Journal of Biological Chemistry

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“…Myristoylation was approximately 10 %. PITPα was expressed in E. coli and purified as described previously [19].…”

Section: Methodsmentioning

confidence: 99%

“…IgE (2 µg\ml final) was added to sensitize the cells for 1 h at 37 mC. The cells were centrifuged at 450 g for 5 min at room temperature and resuspended in Hepes buffer, pH 7.2 (for antigen stimulation), or Pipes buffer, pH 6. supernatant was sampled to assay for released β-hexosaminidase [19]. To monitor the activation of PLD, [$H]choline-labelled cells were used, and release of [$H]choline was monitored as described previously [19].…”

Section: Assays Using Permeabilized Cellsmentioning

confidence: 99%

Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

Way

O'luanaigh

Cockcroft³

2000

Biochem. J.

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The physiological stimulus to exocytosis in mast cells is the crosslinking of the high-affinity IgE receptor, FcεR1, with antigen. We demonstrate a novel function for ADP-ribosylation factor 1 (ARF1) in the regulation of antigen-stimulated secretion using cytosol-depleted RBL-2H3 mast cells for reconstitution of secretory responses. When antigen is used as the stimulus, ARF1 also reconstitutes phospholipase D activation. Using ethanol to divert the phosphatidic acid (the product of phospholipase D activity) to phosphatidylethanol causes inhibition of ARF1-reconstituted secretion. In addition. ARF1 causes an increase in phosphatidylinositol 4,5-bisphosphate (PIP # ) levels at the expense of phosphatidylinositol 4-monophosphate. The requirement for

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“…They regulate the binding of vesicle coat proteins and adaptins [73] and interestingly their addition (together with phospholipase D and the phosphatidylinositol transfer protein, PITP) to permeabilised cell systems results in restoration of vesicle secretory processes [130]. Their function has been mainly studied in relation to movement between Golgi compartments but more recently a role in endosome fusion [131] and recycling from endosomes to the plasma membrane [132] have been reported.…”

Section: Possible Downstream Processesmentioning

confidence: 99%

From receptor to transporter: insulin signalling to glucose transport

1997

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ARF and PITP restore GTPγS-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis

Cited by 164 publications

References 40 publications

Identification and Characterization of a Phosphoinositide Phosphate Kinase Homolog

Identification and Characterization of a Phosphoinositide Phosphate Kinase Homolog

Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

From receptor to transporter: insulin signalling to glucose transport

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