Signaling inositol polyphosphate-5-phosphatase. Characterization of activity and effect of GRB2 association.
An inositol polyphosphate-5-phosphatase (SIP-110) that binds the SH3 domains of the adaptor protein GRB2 was produced in Sf9 cells and characterized. SIP-110 binds to GRB2 in vitro with a stoichiometry of 1 mol of GRB2/0.7 mol of SIP-110. GRB2 binding does not affect enzyme activity implying that GRB2 serves mainly to localize SIP-110 within cells. SIP-110 hydrolyses inositol (Ins)(1,3,4,5)P4 to Ins(1, 3,4)P3. The enzyme does not hydrolyze Ins(1,4,5)P3 that is a substrate for previously described 5-phosphatases nor does it hydrolyze phosphatidylinositol (PtdIns)(4,5)P2. SIP-110 also hydrolyzed PtdIns(3,4,5)P3 to PtdIns(3,4)P2 as did recombinant forms of two other 5-phosphatases designated as inositol polyphosphate-5- phosphatase II, and OCRL (the protein that is mutated in oculocerebrorenal syndrome). The inositol polyphosphate-5-phosphatase enzyme family now is represented by at least 9 distinct genes and includes enzymes that fall into 4 subfamilies based on their activities toward various 5-phosphatase substrates.
Jefferson
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Division of Hematology-Oncology, Washington University School of Medicine, Box 8125, St. Louis, Missouri 63110, USA.
Auethavekiat
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Pot
D A
DA
Williams
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LT
Majerus
P W
PW
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D006358:Hot Temperature; D006868:Hydrolysis; D000072181:Inositol Polyphosphate 5-Phosphatases; D007700:Kinetics; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D018411:Spodoptera; D013379:Substrate Specificity
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D011506:Proteins; D066246:ErbB Receptors; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases