Skip to main content
SpringerLink
Log in

Nucleoside diphosphate kinase as protein histidine kinase

  • Review Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Like phosphorylation of serine, threonine, and tyrosine residues in many organisms, reversible histidine phosphorylation is a well-known regulatory signal in prokaryotes and lower eukaryotes. In vertebrates, phosphohistidine has been mainly described as a phosphorylated intermediate in enzymatic reactions, and it was believed that regulatory histidine phosphorylation is of minor importance. During the last decade, it became evident however, that nucleoside diphosphate kinase (NDPK), an ubiquitously expressed enzyme required for nucleotide homeostasis, can additionally act as a protein histidine kinase. Especially for the isoform NDPK B, at least three defined substrates, the β subunit of heterotrimeric G proteins (Gβ), the intermediate conductance potassium channel KCa3.1, and the Ca2+-conducting TRP channel family member, TRPV5, have been identified. In all three proteins, the phosphorylation of a specific histidine residue is of regulatory importance for protein function, and these phosphohistidines are cleaved by a counteracting 14 kDa phosphohistidine phosphatase (PHP). This article will therefore give an overview of our current knowledge on protein histidine phosphorylation in prokaryotes and lower eukaryotes and compare it with the regulatory phosphorylation and dephosphorylation of histidine residues in vertebrates by NDPK and PHP, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Attwood PV (2013) Histidine kinases from bacteria to humans. Biochem Soc Trans 41:1023–1028

    Article  CAS  PubMed  Google Scholar 

  • Attwood PV, Ludwig K, Bergander K, Besant PG, Adina-Zada A, Krieglstein J, Klumpp S (2010) Chemical phosphorylation of histidine-containing peptides based on the sequence of histone H4 and their dephosphorylation by protein histidine phosphatase. Biochim Biophys Acta 1804:199–205

    Article  CAS  PubMed  Google Scholar 

  • Besant PG, Attwood PV (2005) Mammalian histidine kinases. Biochim Biophys Acta 1754:281–290

    Article  CAS  PubMed  Google Scholar 

  • Boissan M, Dabernat S, Peuchant E, Schlattner U, Lascu I, Lacombe ML (2009) The mammalian Nm23/NDPK family: from metastasis control to cilia movement. Mol Cell Biochem 329:51–62

    Article  CAS  PubMed  Google Scholar 

  • Boyer PD, Deluca M, Ebner KE, Hultquist DE, Peter JB (1962) Identification of phosphohistidine in digests from a probable intermediate of oxidative phosphorylation. J Biol Chem 237:PC3306–PC3308

    CAS  PubMed  Google Scholar 

  • Brokx SJ, Napper S, Wong G, Mirza A, Georges F, Delbaere LT, Waygood EB (1999) Identification of the Escherichia coli enzyme I binding site in histidine-containing protein, HPr, by the effects of mutagenesis. Biochemistry and cell biology =. Biochim Biol Cell 77:507–513

    Article  CAS  Google Scholar 

  • Cai X, Srivastava S, Surindran S, Li Z, Skolnik EY (2014) Regulation of the Epithelial Ca2+ Channel TRPV5 by reversible histidine phosphorylation mediated by NDPK B and PHPT1. Mol Biol Cell 25:1244–1250

  • Casino P, Rubio V, Marina A (2010) The mechanism of signal transduction by two-component systems. Curr Opin Struct Biol 20:763–771

    Article  CAS  PubMed  Google Scholar 

  • Cuello F, Schulze RA, Heemeyer F, Meyer HE, Lutz S, Jakobs KH, Niroomand F, Wieland T (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gβγ dimers and phosphorylation of His-266 in Gβ. J Biol Chem 278:7220–7226

    Article  CAS  PubMed  Google Scholar 

  • de Groot T, Verkaart S, Xi Q, Bindels RJ, Hoenderop JG (2010) The identification of Histidine 712 as a critical residue for constitutive TRPV5 internalization. J Biol Chem 285:28481–28487

    Article  PubMed Central  PubMed  Google Scholar 

  • Declerck N, Dutartre H, Receveur V, Dubois V, Royer C, Aymerich S, van Tilbeurgh H (2001) Dimer stabilization upon activation of the transcriptional antiterminator LicT. J Mol Biol 314:671–681

    Article  CAS  PubMed  Google Scholar 

  • Deutscher J, Francke C, Postma PW (2006) How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol Mol Biol Rev MMBR 70:939–1031

    Article  CAS  Google Scholar 

  • Di L, Srivastava S, Zhdanova O, Sun Y, Li Z, Skolnik EY (2010) Nucleoside diphosphate kinase B knock-out mice have impaired activation of the K+ channel KCa3.1, resulting in defective T cell activation. J Biol Chem 285:38765–38771

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ek P, Pettersson G, Ek B, Gong F, Li JP, Zetterqvist O (2002) Identification and characterization of a mammalian 14-kDa phosphohistidine phosphatase. Eur J Biochem/FEBS 269:5016–5023

    Article  CAS  Google Scholar 

  • Garrett DS, Seok YJ, Peterkofsky A, Gronenborn AM, Clore GM (1999) Solution structure of the 40,000 Mr phosphoryl transfer complex between the N-terminal domain of enzyme I and HPr. Nat Struct Biol 6:166–173

    Article  CAS  PubMed  Google Scholar 

  • Graille M, Zhou CZ, Receveur-Brechot V, Collinet B, Declerck N, van Tilbeurgh H (2005) Activation of the LicT transcriptional antiterminator involves a domain swing/lock mechanism provoking massive structural changes. J Biol Chem 280:14780–14789

    Article  CAS  PubMed  Google Scholar 

  • Grgic I, Eichler I, Heinau P, Si H, Brakemeier S, Hoyer J, Kohler R (2005) Selective blockade of the intermediate-conductance Ca2+-activated K+ channel suppresses proliferation of microvascular and macrovascular endothelial cells and angiogenesis in vivo. Arterioscler Thromb Vasc Biol 25:704–709

    Article  CAS  PubMed  Google Scholar 

  • Han SX, Wang LJ, Zhao J, Zhang Y, Li M, Zhou X, Wang J, Zhu Q (2012) 14-kDa Phosphohistidine phosphatase plays an important role in hepatocellular carcinoma cell proliferation. Oncol Lett 4:658–664

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hess JF, Bourret RB, Simon MI (1988) Histidine phosphorylation and phosphoryl group transfer in bacterial chemotaxis. Nature 336:139–143

    Article  CAS  PubMed  Google Scholar 

  • Hippe HJ, Wieland T (2006) High energy phosphate transfer by NDPK B/Gβγ complexes–an alternative signaling pathway involved in the regulation of basal cAMP production. J Bioenerg Biomembr 38:197–203

    Article  CAS  PubMed  Google Scholar 

  • Hippe HJ, Lutz S, Cuello F, Knorr K, Vogt A, Jakobs KH, Wieland T, Niroomand F (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Specific activation of Gsalpha by an NDPK B.Gβγ complex in H10 cells. J Biol Chem 278:7227–7233

    Article  CAS  PubMed  Google Scholar 

  • Hippe HJ, Luedde M, Lutz S, Koehler H, Eschenhagen T, Frey N, Katus HA, Wieland T, Niroomand F (2007) Regulation of cardiac cAMP synthesis and contractility by nucleoside diphosphate kinase B/G protein βγ dimer complexes. Circ Res 100:1191–1199

    Article  CAS  PubMed  Google Scholar 

  • Hippe HJ, Abu-Taha I, Wolf NM, Katus HA, Wieland T (2011) Through scaffolding and catalytic actions nucleoside diphosphate kinase B differentially regulates basal and β-adrenoceptor-stimulated cAMP synthesis. Cell Signal 23:579–585

    Article  CAS  PubMed  Google Scholar 

  • Kee JM, Muir TW (2012) Chasing phosphohistidine, an elusive sibling in the phosphoamino acid family. ACS Chem Biol 7:44–51

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kennelly PJ, Potts M (1996) Fancy meeting you here! A fresh look at “prokaryotic” protein phosphorylation. J Bacteriol 178:4759–4764

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim Y, Huang J, Cohen P, Matthews HR (1993) Protein phosphatases 1, 2A, and 2C are protein histidine phosphatases. J Biol Chem 268:18513–18518

    CAS  PubMed  Google Scholar 

  • Klumpp S, Hermesmeier J, Selke D, Baumeister R, Kellner R, Krieglstein J (2002) Protein histidine phosphatase: a novel enzyme with potency for neuronal signaling. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 22:1420–1424

    Article  CAS  Google Scholar 

  • Klumpp S, Bechmann G, Maurer A, Selke D, Krieglstein J (2003) ATP-citrate lyase as a substrate of protein histidine phosphatase in vertebrates. Biochem Biophys Res Commun 306:110–115

    Article  CAS  PubMed  Google Scholar 

  • Kohler R, Wulff H, Eichler I, Kneifel M, Neumann D, Knorr A, Grgic I, Kampfe D, Si H, Wibawa J, Real R, Borner K, Brakemeier S, Orzechowski HD, Reusch HP, Paul M, Chandy KG, Hoyer J (2003) Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation 108:1119–1125

    Article  PubMed  Google Scholar 

  • Matthews HR, MacKintosh C (1995) Protein histidine phosphatase activity in rat liver and spinach leaves. FEBS Lett 364:51–54

    Article  CAS  PubMed  Google Scholar 

  • Maurer A, Wieland T, Meissl F, Niroomand F, Mehringer R, Krieglstein J, Klumpp S (2005) The β-subunit of G proteins is a substrate of protein histidine phosphatase. Biochem Biophys Res Commun 334:1115–1120

    Article  PubMed  Google Scholar 

  • Muimo R, Hornickova Z, Riemen CE, Gerke V, Matthews H, Mehta A (2000) Histidine phosphorylation of annexin I in airway epithelia. J Biol Chem 275:36632–36636

    Article  CAS  PubMed  Google Scholar 

  • Pearson RB, Kemp BE (1991) Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol 200:62–81

    Article  CAS  PubMed  Google Scholar 

  • Rosengarth A, Gerke V, Luecke H (2001) X-ray structure of full-length annexin 1 and implications for membrane aggregation. J Mol Biol 306:489–498

    Article  CAS  PubMed  Google Scholar 

  • Schaertl S, Geeves MA, Konrad M (1999) Human nucleoside diphosphate kinase B (Nm23-H2) from melanoma cells shows altered phosphoryl transfer activity due to the S122P mutation. J Biol Chem 274:20159–20164

    Article  CAS  PubMed  Google Scholar 

  • Schneider B, Babolat M, Xu YW, Janin J, Veron M, Deville-Bonne D (2001) Mechanism of phosphoryl transfer by nucleoside diphosphate kinase pH dependence and role of the active site Lys16 and Tyr56 residues. Eur J Biochem / FEBS 268:1964–1971

    Article  CAS  Google Scholar 

  • Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB (1996) Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature 379:369–374

    Article  CAS  PubMed  Google Scholar 

  • Srivastava S, Choudhury P, Li Z, Liu G, Nadkarni V, Ko K, Coetzee WA, Skolnik EY (2006a) Phosphatidylinositol 3-phosphate indirectly activates KCa3.1 via 14 amino acids in the carboxy terminus of KCa3.1. Mol Biol Cell 17:146–154

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Srivastava S, Li Z, Ko K, Choudhury P, Albaqumi M, Johnson AK, Yan Y, Backer JM, Unutmaz D, Coetzee WA, Skolnik EY (2006b) Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Mol Cell 24:665–675

    Article  CAS  PubMed  Google Scholar 

  • Srivastava S, Zhdanova O, Di L, Li Z, Albaqumi M, Wulff H, Skolnik EY (2008) Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc Natl Acad Sci U S A 105:14442–14446

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Srivastava S, Di L, Zhdanova O, Li Z, Vardhana S, Wan Q, Yan Y, Varma R, Backer J, Wulff H, Dustin ML, Skolnik EY (2009) The class II phosphatidylinositol 3 kinase C2beta is required for the activation of the K+ channel KCa3.1 and CD4 T-cells. Mol Biol Cell 20:3783–3791

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Swanson RV, Alex LA, Simon MI (1994) Histidine and aspartate phosphorylation: two-component systems and the limits of homology. Trends Biochem Sci 19:485–490

    Article  CAS  PubMed  Google Scholar 

  • Tharp DL, Wamhoff BR, Turk JR, Bowles DK (2006) Upregulation of intermediate-conductance Ca2+-activated K+ channel (IKCa1) mediates phenotypic modulation of coronary smooth muscle. Am J Physiol Heart Circ Physiol 291:H2493–H2503

    Article  CAS  PubMed  Google Scholar 

  • Toyama K, Wulff H, Chandy KG, Azam P, Raman G, Saito T, Fujiwara Y, Mattson DL, Das S, Melvin JE, Pratt PF, Hatoum OA, Gutterman DD, Harder DR, Miura H (2008) The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans. J Clin Invest 118:3025–3037

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wagner PD, Vu ND (1995) Phosphorylation of ATP-citrate lyase by nucleoside diphosphate kinase. J Biol Chem 270:21758–21764

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Louis JM, Sondej M, Seok YJ, Peterkofsky A, Clore GM (2000) Solution structure of the phosphoryl transfer complex between the signal transducing proteins HPr and IIA(glucose) of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system. EMBO J 19:5635–5649

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xu YW, Morera S, Janin J, Cherfils J (1997) AlF3 mimics the transition state of protein phosphorylation in the crystal structure of nucleoside diphosphate kinase and MgADP. Proc Natl Acad Sci U S A 94:3579–3583

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xu A, Hao J, Zhang Z, Tian T, Jiang S, Hao J, Liu C, Huang L, Xiao X, He D (2010) 14-kDa phosphohistidine phosphatase and its role in human lung cancer cell migration and invasion. Lung Cancer 67:48–56

    Article  PubMed  Google Scholar 

  • Zhang XQ, Sundh UB, Jansson L, Zetterqvist O, Ek P (2009) Immunohistochemical localization of phosphohistidine phosphatase PHPT1 in mouse and human tissues. Ups J Med Sci 114:65–72

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Chemistry and Biochemistry, The University of Western Australia (M310), 35 Stirling Highway, Crawley, WA, 6009, Australia

    Paul V. Attwood

  2. Institute for Experimental and Clinical Pharmacology and Toxicology, Mannheim Medical Faculty, Heidelberg University, Maybachstrasse 14, 68169, Mannheim, Germany

    Thomas Wieland

Authors
  1. Paul V. Attwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Wieland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul V. Attwood.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Attwood, P.V., Wieland, T. Nucleoside diphosphate kinase as protein histidine kinase. Naunyn-Schmiedeberg's Arch Pharmacol 388, 153–160 (2015). https://doi.org/10.1007/s00210-014-1003-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-014-1003-3

Keywords

Search

Navigation