Protein Tyrosine Phosphatases Are Regulated by Mononuclear Iron Dicitrate

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Jun 4

PMID 20519508

Citations 12

Authors

Maria Adelaida Gomez

Laleh Alisaraie

Marina Tiemi Shio

Albert M Berghuis

Colette Lebrun

Isabelle Gautier-Luneau

Martin Olivier

Affiliations

Soon will be listed here.

Abstract

The involvement of macrophages (Mvarphis) as host, accessory, and effector cells in the development of infectious diseases, together with their central role in iron homeostasis, place these immune cells as key players in the interface between iron and infection. Having previously shown that the functional expression of NRAMP-1 results in increased protein phosphorylation mediated in part by an iron-dependent inhibition of Mvarphi protein-tyrosine phosphatase (PTP) activity, we sought to study the mechanism(s) underlying this specific event. Herein we have identified the mononuclear dicitrate iron complex [Fe(cit)(2)H(4-x)]((1+x)-) as the species responsible for the specific inhibition of Mvarphi PTP activity. By using biochemical and computational approaches, we show that [Fe(cit)(2)](5-) targets the catalytic pocket of the PTP SHP-1, competitively inhibiting its interaction with an incoming phosphosubstrate. In vitro and in vivo inhibition of PTP activity by iron-citrate results in protein hyperphosphorylation and enhanced MAPK signaling in response to LPS stimulation. We propose that iron-citrate-mediated PTP inhibition represents a novel and biologically relevant regulatory mechanism of signal transduction.

Citing Articles

Three STEPs forward: A trio of unexpected structures of PTPN5.

Guerrero L, Ebrahim A, Riley B, Kim S, Bishop A, Wu J bioRxiv. 2024; .

PMID: 39605455 PMC: 11601604. DOI: 10.1101/2024.11.20.624168.

Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding Polymer, Attenuates Macrophage Inflammatory Responses.

Ghassemi-Rad J, Fernando W, Holbein B, Hoskin D Adv Pharm Bull. 2023; 13(2):368-377.

PMID: 37342371 PMC: 10278213. DOI: 10.34172/apb.2023.040.

"Ferrocrinology"-Iron Is an Important Factor Involved in Gluco- and Lipocrinology.

Szklarz M, Gontarz-Nowak K, Matuszewski W, Bandurska-Stankiewicz E Nutrients. 2022; 14(21).

PMID: 36364955 PMC: 9654314. DOI: 10.3390/nu14214693.

Iron: Not Just a Passive Bystander in AITD.

Szklarz M, Gontarz-Nowak K, Matuszewski W, Bandurska-Stankiewicz E Nutrients. 2022; 14(21).

PMID: 36364944 PMC: 9658435. DOI: 10.3390/nu14214682.

Protein Tyrosine Phosphatase Inhibition Prevents Experimental Cerebral Malaria by Precluding CXCR3 Expression on T Cells.

Van Den Ham K, Smith L, Richer M, Olivier M Sci Rep. 2017; 7(1):5478.

PMID: 28710387 PMC: 5511231. DOI: 10.1038/s41598-017-05609-1.

References

Burridge K, Nelson A . An in-gel assay for protein tyrosine phosphatase activity: detection of widespread distribution in cells and tissues. Anal Biochem. 1995; 232(1):56-64. DOI: 10.1006/abio.1995.9961. View

Hentze M, Muckenthaler M, Andrews N . Balancing acts: molecular control of mammalian iron metabolism. Cell. 2004; 117(3):285-97. DOI: 10.1016/s0092-8674(04)00343-5. View

Knutson M, Oukka M, Koss L, Aydemir F, Wessling-Resnick M . Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci U S A. 2005; 102(5):1324-8. PMC: 547844. DOI: 10.1073/pnas.0409409102. View

Rarey M, Kramer B, Lengauer T, Klebe G . A fast flexible docking method using an incremental construction algorithm. J Mol Biol. 1996; 261(3):470-89. DOI: 10.1006/jmbi.1996.0477. View

Andersen J, Mortensen O, Peters G, Drake P, Iversen L, Olsen O . Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol Cell Biol. 2001; 21(21):7117-36. PMC: 99888. DOI: 10.1128/MCB.21.21.7117-7136.2001. View

Tonks N . Redox redux: revisiting PTPs and the control of cell signaling. Cell. 2005; 121(5):667-70. DOI: 10.1016/j.cell.2005.05.016. View

Brautigan D, Bornstein P, Gallis B . Phosphotyrosyl-protein phosphatase. Specific inhibition by Zn. J Biol Chem. 1981; 256(13):6519-22. View

Ferguson A, Chakraborty R, Smith B, Esser L, van der Helm D, Deisenhofer J . Structural basis of gating by the outer membrane transporter FecA. Science. 2002; 295(5560):1715-9. DOI: 10.1126/science.1067313. View

Forbes J, Gros P . Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood. 2003; 102(5):1884-92. DOI: 10.1182/blood-2003-02-0425. View

10.

Bilwes A, den Hertog J, Hunter T, Noel J . Structural basis for inhibition of receptor protein-tyrosine phosphatase-alpha by dimerization. Nature. 1996; 382(6591):555-9. DOI: 10.1038/382555a0. View

11.

Schaible U, Kaufmann S . Iron and microbial infection. Nat Rev Microbiol. 2004; 2(12):946-53. DOI: 10.1038/nrmicro1046. View

12.

Markova B, Gulati P, Herrlich P, Bohmer F . Investigation of protein-tyrosine phosphatases by in-gel assays. Methods. 2004; 35(1):22-7. DOI: 10.1016/j.ymeth.2004.07.004. View

13.

Strack V, Krutzfeldt J, Kellerer M, Ullrich A, Lammers R, Haring H . The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta. Biochemistry. 2002; 41(2):603-8. DOI: 10.1021/bi011327v. View

14.

Kakhlon O, Cabantchik Z . The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic Biol Med. 2002; 33(8):1037-46. DOI: 10.1016/s0891-5849(02)01006-7. View

15.

Gautier-Luneau I, Bertet P, Jeunet A, Serratrice G, Pierre J . Iron-citrate complexes and free radicals generation: is citric acid an innocent additive in foods and drinks?. Biometals. 2007; 20(5):793-6. DOI: 10.1007/s10534-006-9042-y. View

16.

Dadke S, Kusari A, Kusari J . Phosphorylation and activation of protein tyrosine phosphatase (PTP) 1B by insulin receptor. Mol Cell Biochem. 2001; 221(1-2):147-54. DOI: 10.1023/a:1010909031310. View

17.

Wojciechowski W, DeSanctis J, Skamene E, Radzioch D . Attenuation of MHC class II expression in macrophages infected with Mycobacterium bovis bacillus Calmette-Guérin involves class II transactivator and depends on the Nramp1 gene. J Immunol. 1999; 163(5):2688-96. View

18.

Vidal S, Tremblay M, Govoni G, Gauthier S, Sebastiani G, Malo D . The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J Exp Med. 1995; 182(3):655-66. PMC: 2192162. DOI: 10.1084/jem.182.3.655. View

19.

Yang J, Liang X, Niu T, Meng W, Zhao Z, Zhou G . Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1. J Biol Chem. 1998; 273(43):28199-207. DOI: 10.1074/jbc.273.43.28199. View

20.

Jaramillo M, Godbout M, Olivier M . Hemozoin induces macrophage chemokine expression through oxidative stress-dependent and -independent mechanisms. J Immunol. 2004; 174(1):475-84. DOI: 10.4049/jimmunol.174.1.475. View