Requirement for Phosphatidylinositol Transfer Protein in Epidermal Growth Factor Signaling

Kauffmann‐Zeh, Andrea; Thomas, Geraint M. H.; Ball, Andrew; Prosser, Simon; Cunningham, Emer; Cockcroft, Shamshad; Hsuan, J. Justin

doi:10.1126/science.7761838

Cited by 176 publications

(118 citation statements)

References 35 publications

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“…The ability of PITPα to replace ARF1 in the reconstitution assay provides further support for the hypothesis that PIP # is required for exocytosis. PITPα is also required for the synthesis of PIP # as a substrate for PLCs [22,43], in the Ca# + -stimulated exocytotic pathway in PC12 cells [44,45], and for vesicle formation ( [46] ; reviewed in [47]). Interestingly, PITPα and ARF1 can be functionally exchanged in the vesicle formation assay, just as in the secretory reconstitution assays presented here.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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 greatest demand for PtdIns comes from PLC-mediated hydrolysis of PtdIns(4,5)P # , which can occur in multiple compartments including the plasma membrane and the nucleus. Thus PLCmediated hydrolysis of PtdIns(4,5)P # is dependent on the availability of PITP, whatever the mode of activation of the PLC [15][16][17][18]. PtdIns(4,5)P # is also used as a substrate by phosphoinositide 3-kinase ; again, PITP has been identified as a requirement for this signalling pathway [19].…”

Section: Introductionmentioning

confidence: 99%

Purification and cloning of phosphatidylinositol transfer proteins from Dictyostelium discoideum: homologues of both mammalian PITPs and Saccharomyces cerevisiae Sec14p are found in the same cell

Swigart

Insall

Cockcroft

2000

Biochemical Journal

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Soluble phosphatidylinositol transfer proteins (PITPs) have important roles in lipid-mediated signalling as well as in membrane traffic. Two PITPs (α and β) have been cloned from mammalian cells, which are unrelated in sequence to yeast PITP (the product of the SEC14 gene). However, all three PITPs can perform interchangeably to reconstitute function in mammalian cells. We have now purified the major PITP from the cytoplasm of Dictyostelium discoideum and cloned the gene. This protein, DdPITP1, is homologous with mammalian PITPα and PITPβ. We have also cloned a second gene (DdPITP2) related in sequence to DdPITP1. In addition, an independently cloned cDNA encodes a relative of the SEC14 family of yeast PITPs. DdPITP1, DdPITP2 and DdSec14 proteins were all able to mediate the transfer of PtdIns from one membrane compartment to another; they thus exhibited the hallmark of PITPs. Secondly, all three PITPs were able to rescue phospholipase C-mediated phosphoinositide hydrolysis in PITP-depleted HL60 cells, indicating that all three PITPs were capable of stimulating phosphoinositide synthesis. The identification of PITPs related to both mammalian PITPs and yeast Sec14p in a single organism will provide a unique opportunity to examine the functions of this class of protein with genetic approaches.

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“…PITP might provide this protection. We note that in A431 cells and HL60 cells, permeabilized by SLO, most of the PITPα is lost within 5 min [46,47]. Moreover, the PITPs applied at relevant physiological concentrations oppose the inhibition due to neomycin.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells

Pinxteren¹,

Hammond²,

Thomas³

2001

Biochemical Journal

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Mast cells permeabilized by streptolysin O undergo exocytosis when stimulated with Ca# + and guanosine 5h-[γ-thio]triphosphate but become progressively refractory to this stimulus if it is delayed. This run-down of responsiveness occurs over a period of 20-30 min, during which the cells leak soluble and tethered proteins. We show here that withdrawal of ATP during the process of run-down is strongly inhibitory but that as little as 25 µM ATP can extend responsiveness significantly ; this effect is maximal at 50 µM. When phosphatidylinositol transfer proteins (PITPs) are provided to cells at the time of permeabilization, rundown is retarded. We conclude that in the presence of ATP they convey substrates for phosphorylation that are essential for exocytosis and thus interact with the regulatory machinery. Furthermore, we show that PITPα and PITPβ have additive effects in this mechanism, suggesting that they are not functionally redundant. Alternatively, secretion from run-down cells can be

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Requirement for Phosphatidylinositol Transfer Protein in Epidermal Growth Factor Signaling

Cited by 176 publications

References 35 publications

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

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

Purification and cloning of phosphatidylinositol transfer proteins from Dictyostelium discoideum: homologues of both mammalian PITPs and Saccharomyces cerevisiae Sec14p are found in the same cell

Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells

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