Metabolic switching of PI3K-dependent lipid signals

Pete Downes, N. R. Leslie, I. H. Batty, J. van der Kaay

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    The lipid phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10), is the product of a major tumour suppressor gene that antagonizes PI3K (phosphoinositide 3-kinase) signalling by dephosphorylating the 3-position of the inositol ring of PtdIns(3,4,5)P(3). PtdIns(3,4,5)P(3) is also metabolized by removal of the 5-phosphate catalysed by a distinct family of enzymes exemplified by SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] and SHIP2. Mouse knockout studies, however, suggest that PTEN and SHIP2 have profoundly different biological functions. One important reason for this is likely to be that SHIP2 exists in a relatively inactive state until cells are exposed to growth factors or other stimuli. Hence, regulation of SHIP2 is geared towards stimulus dependent antagonism of PI3K signalling. PTEN, on the other hand, appears to be active in unstimulated cells and functions to maintain basal PtdIns(3,4,5)P(3) levels below the critical signalling threshold. We suggest that concomitant inhibition of cysteine-dependent phosphatases, such as PTEN, with activation of SHIP2 functions as a metabolic switch to regulate independently the relative levels of PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2).
    Original languageEnglish
    Pages (from-to)188-192
    Number of pages5
    JournalBiochemical Society Transactions
    Volume35
    Issue number 2
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    1-Phosphatidylinositol 4-Kinase
    Phosphatidylinositols
    Phosphotransferases
    Lipids
    Phosphoric Monoester Hydrolases
    PTEN Phosphohydrolase
    Chromosomes, Human, Pair 10
    Inositol
    Tumor Suppressor Genes
    Knockout Mice
    Cysteine
    Intercellular Signaling Peptides and Proteins
    Phosphates
    Phosphatases
    Chromosomes
    Enzymes
    Tumors
    Genes
    Chemical activation
    Switches

    Keywords

    • Acid Anhydride Hydrolases
    • Homeostasis
    • Humans
    • Inositol Phosphates
    • Leptin
    • Lipids
    • Mutation
    • Oxidative Stress
    • PTEN Phosphohydrolase
    • Phosphatidylinositol 3-Kinases
    • Phosphoproteins
    • Phosphoric Monoester Hydrolases
    • Signal Transduction

    Cite this

    Downes, P., Leslie, N. R., Batty, I. H., & van der Kaay, J. (2007). Metabolic switching of PI3K-dependent lipid signals. Biochemical Society Transactions, 35( 2), 188-192. https://doi.org/10.1042/BST0350188
    Downes, Pete ; Leslie, N. R. ; Batty, I. H. ; van der Kaay, J. / Metabolic switching of PI3K-dependent lipid signals. In: Biochemical Society Transactions. 2007 ; Vol. 35, No. 2. pp. 188-192.
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    abstract = "The lipid phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10), is the product of a major tumour suppressor gene that antagonizes PI3K (phosphoinositide 3-kinase) signalling by dephosphorylating the 3-position of the inositol ring of PtdIns(3,4,5)P(3). PtdIns(3,4,5)P(3) is also metabolized by removal of the 5-phosphate catalysed by a distinct family of enzymes exemplified by SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] and SHIP2. Mouse knockout studies, however, suggest that PTEN and SHIP2 have profoundly different biological functions. One important reason for this is likely to be that SHIP2 exists in a relatively inactive state until cells are exposed to growth factors or other stimuli. Hence, regulation of SHIP2 is geared towards stimulus dependent antagonism of PI3K signalling. PTEN, on the other hand, appears to be active in unstimulated cells and functions to maintain basal PtdIns(3,4,5)P(3) levels below the critical signalling threshold. We suggest that concomitant inhibition of cysteine-dependent phosphatases, such as PTEN, with activation of SHIP2 functions as a metabolic switch to regulate independently the relative levels of PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2).",
    keywords = "Acid Anhydride Hydrolases, Homeostasis, Humans, Inositol Phosphates, Leptin, Lipids, Mutation, Oxidative Stress, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphoric Monoester Hydrolases, Signal Transduction",
    author = "Pete Downes and Leslie, {N. R.} and Batty, {I. H.} and {van der Kaay}, J.",
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    Downes, P, Leslie, NR, Batty, IH & van der Kaay, J 2007, 'Metabolic switching of PI3K-dependent lipid signals', Biochemical Society Transactions, vol. 35, no. 2, pp. 188-192. https://doi.org/10.1042/BST0350188

    Metabolic switching of PI3K-dependent lipid signals. / Downes, Pete; Leslie, N. R.; Batty, I. H.; van der Kaay, J.

    In: Biochemical Society Transactions, Vol. 35, No. 2, 2007, p. 188-192.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Metabolic switching of PI3K-dependent lipid signals

    AU - Downes, Pete

    AU - Leslie, N. R.

    AU - Batty, I. H.

    AU - van der Kaay, J.

    PY - 2007

    Y1 - 2007

    N2 - The lipid phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10), is the product of a major tumour suppressor gene that antagonizes PI3K (phosphoinositide 3-kinase) signalling by dephosphorylating the 3-position of the inositol ring of PtdIns(3,4,5)P(3). PtdIns(3,4,5)P(3) is also metabolized by removal of the 5-phosphate catalysed by a distinct family of enzymes exemplified by SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] and SHIP2. Mouse knockout studies, however, suggest that PTEN and SHIP2 have profoundly different biological functions. One important reason for this is likely to be that SHIP2 exists in a relatively inactive state until cells are exposed to growth factors or other stimuli. Hence, regulation of SHIP2 is geared towards stimulus dependent antagonism of PI3K signalling. PTEN, on the other hand, appears to be active in unstimulated cells and functions to maintain basal PtdIns(3,4,5)P(3) levels below the critical signalling threshold. We suggest that concomitant inhibition of cysteine-dependent phosphatases, such as PTEN, with activation of SHIP2 functions as a metabolic switch to regulate independently the relative levels of PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2).

    AB - The lipid phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10), is the product of a major tumour suppressor gene that antagonizes PI3K (phosphoinositide 3-kinase) signalling by dephosphorylating the 3-position of the inositol ring of PtdIns(3,4,5)P(3). PtdIns(3,4,5)P(3) is also metabolized by removal of the 5-phosphate catalysed by a distinct family of enzymes exemplified by SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] and SHIP2. Mouse knockout studies, however, suggest that PTEN and SHIP2 have profoundly different biological functions. One important reason for this is likely to be that SHIP2 exists in a relatively inactive state until cells are exposed to growth factors or other stimuli. Hence, regulation of SHIP2 is geared towards stimulus dependent antagonism of PI3K signalling. PTEN, on the other hand, appears to be active in unstimulated cells and functions to maintain basal PtdIns(3,4,5)P(3) levels below the critical signalling threshold. We suggest that concomitant inhibition of cysteine-dependent phosphatases, such as PTEN, with activation of SHIP2 functions as a metabolic switch to regulate independently the relative levels of PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2).

    KW - Acid Anhydride Hydrolases

    KW - Homeostasis

    KW - Humans

    KW - Inositol Phosphates

    KW - Leptin

    KW - Lipids

    KW - Mutation

    KW - Oxidative Stress

    KW - PTEN Phosphohydrolase

    KW - Phosphatidylinositol 3-Kinases

    KW - Phosphoproteins

    KW - Phosphoric Monoester Hydrolases

    KW - Signal Transduction

    U2 - 10.1042/BST0350188

    DO - 10.1042/BST0350188

    M3 - Article

    VL - 35

    SP - 188

    EP - 192

    JO - Biochemical Society Transactions

    JF - Biochemical Society Transactions

    SN - 0300-5127

    IS - 2

    ER -