The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2

Dyson, Jennifer M; Kong, Anne Mandy; Wiradjaja, Fenny; Astle, Megan V.; Gurung, Rajendra; Mitchell, Christina A.

doi:10.1016/j.biocel.2005.05.003

Cited by 51 publications

(53 citation statements)

References 22 publications

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“…SHIP2, a phosphatase for the five phosphoryl group on the signaling lipid PtdIns 3,4,5 trisphosphate, showed an eightfold increase in phosphorylation on Tyr 887, another site not previously identified as responsive to insulin. SHIP2 binds to SHC, and may participate in shutting down insulin signaling through the PI3K/Akt pathway (28). Nck 1 and 2, closely related adaptor proteins that bind to IRS-1 and may serve as a link to the cytoskeleton (29,30), increased in tyrosine phosphorylation on a single site ϳ1.8-fold.…”

Section: Resultsmentioning

confidence: 99%

Temporal Dynamics of Tyrosine Phosphorylation in Insulin Signaling

et al. 2006

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The insulin-signaling network regulates blood glucose levels, controls metabolism, and when dysregulated, may lead to the development of type 2 diabetes. Although the role of tyrosine phosphorylation in this network is clear, only a limited number of insulin-induced tyrosine phosphorylation sites have been identified. To address this issue and establish temporal response, we have, for the first time, carried out an extensive, quantitative, mass spectrometrybased analysis of tyrosine phosphorylation in response to insulin. The study was performed with 3T3-L1 adipocytes stimulated with insulin for 0, 5, 15, and 45 min. It has resulted in the identification and relative temporal quantification of 122 tyrosine phosphorylation sites on 89 proteins. Insulin treatment caused a change of at least 1.3-fold in tyrosine phosphorylation on 89 of these sites. Among the responsive sites, 20 were previously known to be tyrosine phosphorylated with insulin treatment, including sites on the insulin receptor and insulin receptor substrate-1. The remaining 69 responsive sites have not previously been shown to be altered by insulin treatment. They were on proteins with a wide variety of functions, including components of the trafficking machinery for the insulin-responsive glucose transporter GLUT4. These results show that insulin-elicited tyrosine phosphorylation is extensive and implicate a number of hitherto unrecognized proteins in insulin action. Diabetes 55:2171-2179, 2006 M etabolic control is primarily regulated by the insulin-signaling network. In healthy individuals, insulin stimulates glucose uptake from the bloodstream into adipose tissue and skeletal muscle while inhibiting glucose production in the liver. Dysregulation of this network associated with insulin resistance causes an increase in blood glucose and lipid levels, often initially associated with an increase in insulin levels and eventually culminating in type 2 diabetes (1). Understanding the signaling network activated by insulin stimulation is crucial for identifying the causes and effects of network dysregulation and insulin resistance.Insulin binds to the insulin receptor at the cell surface and activates its tyrosine kinase activity, leading to autophosphorylation and phosphorylation of several receptor substrates. Phosphorylation of selected tyrosine sites on receptor substrates is known to activate different pathways leading to increased glucose uptake, lipogenesis, and glycogen and protein synthesis, as well as to stimulation of cell growth (1,2). In addition to activation of these pathways by tyrosine phosphorylation, several mechanisms of downregulating the response to insulin stimulation have also been identified. For instance, serine phosphorylation on insulin receptor substrate (IRS)-1 induced by a variety of factors has been shown to interfere with the activating effects of tyrosine phosphorylation by decreasing binding to the insulin receptor or increasing degradation of IRS-1 (1,3,4). Ser/Thr phosphorylation of the insulin receptor has also bee...

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Section: Resultsmentioning

confidence: 99%

Temporal Dynamics of Tyrosine Phosphorylation in Insulin Signaling

et al. 2006

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“…SKIP is localized in endoplasmic reticulum and the Golgi compartment under resting conditions and is translocated to the plasma membrane when the cells are exposed to insulin (10,12). On the other hand, SHIP2 possesses an SH2 domain at the N terminus that interacts with other signaling molecules such as Shc and p130 cas and a proline-rich domain at the C terminus that interacts with Abl and Shc (7). Unlike SKIP and SHIP2, PTEN is a PtdIns(3,4,5)P 3 3-phosphatase with a C-terminal C2 domain for binding to phospholipids (5).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, SKIP may be a potential therapeutic target for obesity and type II diabetes. Although PTEN and SHIP2 may also be good candidates, targeting these proteins may be problematic because PTEN is a tumor suppressor, and a SHIP2 deficiency causes severe growth retardation (7,22). In contrast, Pps Brdm1 /ϩ mice did not appear to show increased cancer susceptibility over a 1-year observation period or to demonstrate severe growth retardation.…”

Section: Discussionmentioning

confidence: 99%

Increased Insulin Action in SKIP Heterozygous Knockout Mice

Ijuin

Mizutani

et al. 2008

Molecular and Cellular Biology

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“…Interestingly, we found that CD2AP bound to SH2-domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2), a negative regulator of insulin signalling and a molecule associated with the metabolic syndrome (Dyson et al 2005). Lipid phosphatase SHIP2 downregulates PI3K mediated signalling, induced by insulin and other growth factors, by hydrolyzing PI(3,4,5,)P 3 to PI(3,4)P 2 (Blero et al 2001.…”

Section: Introductionmentioning

confidence: 99%

Lipid phosphatase SHIP2 downregulates insulin signalling in podocytes

Hyvönen

Saurus

Wasik

et al. 2010

Molecular and Cellular Endocrinology

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Please cite this article as: Hyvönen, M.E., Saurus, P., Wasik, A., Heikkilä, E., Havana, M., Trokovic, R., Saleem, M., Holthöfer, H., Lehtonen, S., Lipid phosphatase SHIP2 downregulates insulin signalling in podocytes, Molecular and Cellular Endocrinology (2010), doi:10.1016/j.mce.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. downregulates insulin signalling in podocytes. The upregulation of SHIP2 in Zucker rat glomeruli prior to the age of onset of proteinuria suggests a possible role for SHIP2 in the development of podocyte injury.

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The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2

Cited by 51 publications

References 22 publications

Temporal Dynamics of Tyrosine Phosphorylation in Insulin Signaling

Temporal Dynamics of Tyrosine Phosphorylation in Insulin Signaling

Increased Insulin Action in SKIP Heterozygous Knockout Mice

Lipid phosphatase SHIP2 downregulates insulin signalling in podocytes

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