Characterization of the substrate specificity of the inositol 5-phosphatase SHIP1

Nina Nelson; Torsten Wundenberg; Hongying Lin; Christoph Rehbach; Stefan Horn; Sabine Windhorst; Manfred Jücker

doi:10.1016/j.bbrc.2020.01.012

Characterization of the substrate specificity of the inositol 5-phosphatase SHIP1

Biochem Biophys Res Commun. 2020 Apr 2;524(2):366-370. doi: 10.1016/j.bbrc.2020.01.012. Epub 2020 Jan 28.

Authors

Nina Nelson¹, Torsten Wundenberg¹, Hongying Lin, Christoph Rehbach¹, Stefan Horn², Sabine Windhorst¹, Manfred Jücker³

Affiliations

¹ Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
² Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany; Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
³ Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. Electronic address: [email protected].

PMID: 32005521
DOI: 10.1016/j.bbrc.2020.01.012

Abstract

SHIP1 is an inositol 5-phosphatase which is well established for its tumour suppressor potential in leukaemia. Enzymatically, two SHIP1 substrates, PtdIns(3,4,5)P₃ and Ins(1,3,4,5)P₄ have been identified to date. Additional substrates were found for the homologue SHIP2. In this study, we identified new inositol phosphate (InsP) substrates of SHIP1 by metal dye detection high-performance liquid chromatography and compared the substrate profiles of SHIP1 and SHIP2. We were able to verify Ins(1,3,4,5)P₄ as a substrate of SHIP1 and interestingly found Ins(1,2,3,4,5)P₅ and Ins(2,3,4,5)P₄ to be preferably used as substrates and Ins(1,4,5,6)P₄ and Ins(2,4,5,6)P₄ to be weak substrates. All of those except Ins(2,3,4,5)P₄ are also known substrates of SHIP2 indicating a possible exclusive role of Ins(2,3,4,5)P₄ hydrolysis for SHIP1 but not SHIP2 function.

Keywords: Inositol 5-phosphatase; Inositol phosphate; SHIP1.

MeSH terms

Enzyme Assays
Humans
Inositol Phosphates / chemistry
Inositol Phosphates / metabolism*
Kinetics
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / metabolism*
Recombinant Proteins / metabolism
Substrate Specificity

Substances

Inositol Phosphates
Recombinant Proteins
INPP5D protein, human
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases