Phosphokinome Analysis of Barth Syndrome Lymphoblasts Identify Novel Targets in the Pathophysiology of the Disease

International Journal of Molecular Sciences
Prasoon AgarwalGrant M Hatch

Abstract

Barth Syndrome (BTHS) is a rare X-linked genetic disease in which the specific biochemical deficit is a reduction in the mitochondrial phospholipid cardiolipin (CL) as a result of a mutation in the CL transacylase tafazzin. We compared the phosphokinome profile in Epstein-Barr-virus-transformed lymphoblasts prepared from a BTHS patient with that of an age-matched control individual. As expected, mass spectrometry analysis revealed a significant (>90%) reduction in CL in BTHS lymphoblasts compared to controls. In addition, increased oxidized phosphatidylcholine (oxPC) and phosphatidylethanolamine (PE) levels were observed in BTHS lymphoblasts compared to control. Given the broad shifts in metabolism associated with BTHS, we hypothesized that marked differences in posttranslational modifications such as phosphorylation would be present in the lymphoblast cells of a BTHS patient. Phosphokinome analysis revealed striking differences in the phosphorylation levels of phosphoproteins in BTHS lymphoblasts compared to control cells. Some phosphorylated proteins, for example, adenosine monophosphate kinase, have been previously validated as bonafide modified phosphorylation targets observed in tafazzin deficiency or under conditions of r...Continue Reading

References

Jan 1, 1994·The Biochemical Journal·G M Hatch
Dec 31, 1997·The Journal of Biological Chemistry·H ItoK Kato
Dec 19, 2000·Biochemical and Biophysical Research Communications·P VrekenP G Barth
Jul 12, 2002·Annals of Neurology·Michael SchlameThomas J J Blanck
May 14, 2003·Proceedings of the National Academy of Sciences of the United States of America·Grzegorz SowaWilliam C Sessa
Oct 11, 2003·The Journal of Biological Chemistry·Yang XuMichael Schlame
Aug 19, 2004·Journal of Cell Science·Kelian ChenBrian W Howell
Apr 5, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yang XuMichael Schlame
Apr 13, 2005·Journal of Proteome Research·Joseph A DeGiorgisAyse Dosemeci
Jan 31, 2006·Progress in Lipid Research·Kristin D Hauff, Grant M Hatch
Aug 11, 2006·American Journal of Physiology. Cell Physiology·Adam J Chicco, Genevieve C Sparagna
Sep 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Zhidan WuSusan C Stevenson
Nov 4, 2006·The Journal of Biological Chemistry·Yang XuMichael Schlame
Dec 22, 2006·The Journal of Biological Chemistry·Monica L FriedrichCraig M Walsh
Feb 16, 2008·The Journal of Clinical Investigation·Karl BalabanianFrançoise Bachelerie
Apr 4, 2008·Cellular and Molecular Life Sciences : CMLS·A BaruzziG Berton
Apr 24, 2008·Molecular Microbiology·Shuliang ChenMiriam L Greenberg
Jan 27, 2009·Molecular Biotechnology·John Geraldine Sandana Mala, Satoru Takeuchi
Mar 30, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Quan He
Aug 17, 2010·Protein Expression and Purification·Anastasia F ThéveninRoberta F Colman
Jan 22, 2011·Neurochemical Research·Takao HondaKazunori Nakajima
Jan 27, 2011·Science Signaling·Richard Berry
Apr 22, 2011·The Journal of Biological Chemistry·Lan ChengGlenn L Radice
Nov 2, 2012·The Journal of Biological Chemistry·Yejing Ge, Jie Chen
Jan 29, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maitham KhajahDonna-Marie McCafferty
Mar 8, 2013·Biochimica Et Biophysica Acta·Bénédicte DemeulderLuc Bertrand
May 15, 2013·Mitochondrion·Rita FerreiraM Rosário Domingues
Jun 15, 2013·Progress in Molecular Biology and Translational Science·Melanie PhilippMarc G Caron

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Citations

Jan 9, 2021·Molecular and Cellular Biochemistry·Hana M Zegallai, Grant M Hatch

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Methods Mentioned

BETA
transacylation
chip

Software Mentioned

Kinections Pathway Map
PhosphoSitePlus

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