Signaling inositol polyphosphate-5-phosphatase. Characterization of activity and effect of GRB2 association.

Abstract

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.

• Authors: A B Jefferson, V Auethavekiat, D A Pot, L T Williams, P W Majerus
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 272 Issue 9 Pg. 5983-8 (Feb 28 1997) ISSN: 0021-9258 [Print] United States
• PMID: 9038219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adaptor Proteins, Signal Transducing
• GRB2 Adaptor Protein
• Proteins
• ErbB Receptors
• Phosphoric Monoester Hydrolases
• Inositol Polyphosphate 5-Phosphatases

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Chromatography, High Pressure Liquid
• ErbB Receptors (metabolism)
• GRB2 Adaptor Protein
• Hot Temperature
• Hydrolysis
• Inositol Polyphosphate 5-Phosphatases
• Kinetics
• Phosphoric Monoester Hydrolases (metabolism)
• Proteins (metabolism)
• Spodoptera
• Substrate Specificity