Regulation of phosphoinositide signaling by the inositol polyphosphate 5‐phosphatases

Astle, Megan V.; Seaton, Gillian; Davies, Elizabeth M.; Fedele, Clare G.; Rahman, Parvin; Arsala, Laima; Mitchell, Christina A.

doi:10.1080/15216540600871159

Cited by 45 publications

(58 citation statements)

References 29 publications

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“…Recently, mutations in this gene have also been described in patients with Dent disease, a condition involving kidney reabsorption defects similar to those observed in Lowe syndrome [2]. Inositol 5-phosphtases dephosphorylate the five position of inositol polyphosphates and of phosphoinositides [3]. Phosphoinositides are phosphorylated metabolites of phosphatidylinositol and play a key role in cell physiology, including signaling, cytoskeletal regulation, and membrane traffic [4].…”

Section: Introductionmentioning

confidence: 96%

All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding

McCrea

Paradise

Tomasini

et al. 2008

Biochemical and Biophysical Research Communications

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Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, an X-linked disorder characterized by bilateral cataracts, mental retardation, neonatal hypotonia, and renal Fanconi syndrome, and for Dent disease, another X-linked condition characterized by kidney reabsorption defects. We have previously described an interaction of OCRL with the endocytic adaptor APPL1 that links OCRL to protein networks involved in the disease phenotype. Here we provide new evidence showing that among the interactions which target OCRL to membranes of the endocytic pathway, binding to APPL1 is the only one abolished by all known disease-causing missense mutations in the ASH-RhoGAP domains of the protein. Furthermore, we demonstrate that APPL1 and rab5 independently contribute to recruit OCRL to enlarged endosomes induced by the expression of constitutively active Rab5. Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease.

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Section: Introductionmentioning

confidence: 96%

All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding

McCrea

Paradise

Tomasini

et al. 2008

Biochemical and Biophysical Research Communications

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“…Each PI species is produced and converted to another PI species by strictly regulated phosphorylation and dephosphorylation on the inositol ring through PI-specific kinases and phosphatases, respectively. [1][2][3][4] PIs function as an intracellular signaling molecules and regulate diverse cellular functions including proliferation, apoptosis and motility; therefore impaired PI turnover due to the malfunction of responsible PI kinase(s)/phosphatase(s) gives severe impacts on a wide variety of intracellular signaling systems and potentially becomes causal factors for certain human diseases. [5][6][7][8][9][10] Phosphatase and tensin homolog (PTEN) exhibits PI phosphatase activity towards phosphatidylinositol 3,4,5-trisphosphate (PIP3), 4,11,12) which is produced by phosphatidylinositol 3-kinase (PI3K) upon growth factor stimulation and displays robust effects on multiple cellular events including proliferation and apoptosis (Fig.…”

Section: Introductionmentioning

confidence: 99%

PTEN: Its Deregulation and Tumorigenesis

Maehama

2007

Biological & Pharmaceutical Bulletin

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The tumor suppressor phosphatase and tensin homolog (PTEN) functions as a phosphoinositide 3-phosphatase, that antagonizes phosphatidylinositol 3-kinase action, and negatively regulates cell proliferation and survival signals. Inactivation of PTEN by loss-of-function mutations gives rise to deregulated hyperproliferation of cells, leading to oncogenic transformation. Recent studies have identified a number of upstream regulatory factors for PTEN and unveiled that the impairment in the PTEN regulatory system potentially becomes a causal factor for oncogenic transformation of cells. This article will review the PTEN inactivation mechanism which is linked to human tumorigenesis, particularly focusing on recent research progress in PTEN regulators.

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“…Running title: Inpp5k and the control of renal water transport Eileen Pernot 1,2,7 , Sara Terryn 4,7 , Siew Chiat Cheong Inositol Phosphatase, and Pps, for Putative Phosphatase) [2,7,30,32,33]. These enzymes tightly control the level of the above-mentioned phosphoinositides in a tissue-, cellular-, subcellular-and signalling cascade-specific way.…”

Section: The Inositol Inpp5k 5-phosphatase Affects Osmoregulation Thrmentioning

confidence: 99%

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

Pernot

Terryn

Cheong

et al. 2011

Pflugers Arch - Eur J Physiol

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Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts. [13,17, 29, 40]. It also regulates the activity of many ion channels and transporters [35,36]. PtdIns(4,5)P2 is mainly localized in the inner leaflet of plasma membranes, but smaller pools have been detected in intracellular membranes, including Golgi, endoplasmic reticulum, endosomes and lamellipodia [13]. Mechanistically, a very large number of proteins are recruited to PtdIns(4,5)P2 via pleckstrin homology (PH), phagocyte oxidase (PX), Fab1p, YOTB, Vac1p and EEA1 (FYVE), epsin N-terminal homology (ENTH) domains or through small patches of basic amino acids [13,18, 28]. PtdIns(4,5,)P2 also serves as precursor of five essential signalling molecules: diacylglycerol, inositol (1,4,5)-trisphosphate, PtdIns4P, PtdIns5P and PtdIns(3,4,5)P3 [13,17]. In non stimulated cells, PtdIns(3,4,5)P3 levels are very low in the plasma membrane, reaching ~0.1% of the level of PtdIns(4,5)P2 [13,17]. Upon cell activation, PtdIns(3,4,5)P3 levels are transiently increased by a factor ranging from 2-to 100-fold. This phosphoinositide is implicated in the control of cell survival, growth and proliferation, resistance to apoptosis, regulation of cytoskeleton dynamics, membrane trafficking, cell migration, and many of the metabolic responses to insulin [12,13].PtdIns(3,4,5)P3 regulates a wide variety of effector proteins primarily by binding and recruiting specific proteins.In mammalian cells, PtdIns(4,5)P2 and/or PtdIns(3,4,5)P3 are substrates for several members of the phosphoinositide 5-phosphatases family, including Inppl1 (or

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Regulation of phosphoinositide signaling by the inositol polyphosphate 5‐phosphatases

Cited by 45 publications

References 29 publications

All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding

All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding

PTEN: Its Deregulation and Tumorigenesis

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

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