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Alterations in reversible protein histidine phosphorylation as intracellular signals in cardiovascular disease.

Wieland T, Attwood PV - Front Pharmacol (2015)

Bottom Line: More recently, it has become evident that the nucleoside diphosphate kinase isoform B (NDPK-B), an ubiquitously expressed enzyme involved in nucleotide metabolism, and a highly specific phosphohistidine phosphatase (PHP) form a regulatory histidine protein kinase/phosphatase system in mammals.At least three well defined substrates of NDPK-B are known: The β-subunit of heterotrimeric G-proteins (Gβ), the intermediate conductance potassium channel SK4 and the Ca(2+) conducting TRP channel family member, TRPV5.In each of these proteins the phosphorylation of a specific histidine residue regulates cellular signal transduction or channel activity.

View Article: PubMed Central - PubMed

Affiliation: Institute for Experimental and Clinical Pharmacology and Toxicology, Mannheim Medical Faculty, Heidelberg University , Mannheim, Germany.

ABSTRACT
Reversible phosphorylation of amino acid side chains in proteins is a frequently used mechanism in cellular signal transduction and alterations of such phosphorylation patterns are very common in cardiovascular diseases. They reflect changes in the activities of the protein kinases and phosphatases involving signaling pathways. Phosphorylation of serine, threonine, and tyrosine residues has been extensively investigated in vertebrates, whereas reversible histidine phosphorylation, a well-known regulatory signal in lower organisms, has been largely neglected as it has been generally assumed that histidine phosphorylation is of minor importance in vertebrates. More recently, it has become evident that the nucleoside diphosphate kinase isoform B (NDPK-B), an ubiquitously expressed enzyme involved in nucleotide metabolism, and a highly specific phosphohistidine phosphatase (PHP) form a regulatory histidine protein kinase/phosphatase system in mammals. At least three well defined substrates of NDPK-B are known: The β-subunit of heterotrimeric G-proteins (Gβ), the intermediate conductance potassium channel SK4 and the Ca(2+) conducting TRP channel family member, TRPV5. In each of these proteins the phosphorylation of a specific histidine residue regulates cellular signal transduction or channel activity. This article will therefore summarize our current knowledge on protein histidine phosphorylation and highlight its relevance for cardiovascular physiology and pathophysiology.

No MeSH data available.


Related in: MedlinePlus

Structures of the three forms of phosphohistidine: (A) 1-phosphohistidine; (B) 3-phosphohistidine; (C) 1,3-diphosphohistidine.
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Figure 1: Structures of the three forms of phosphohistidine: (A) 1-phosphohistidine; (B) 3-phosphohistidine; (C) 1,3-diphosphohistidine.

Mentions: Phosphohistidine has a number of attributes that make it different from the phosphoester phosphoamino acids. The phosphoryl group is bonded to the imidazole ring of the amino acid via a phosphoramidate bond. Since the imidazole ring contains two nitrogens, there are three forms of phosphohistidine, 1- or 3-phosphohistidine or 1,3-diphosphohistidine (see Figure 1). The two forms of monophosphohistidine are both known to occur in cellular proteins (Walinder, 1969b; Chen et al., 1977; Fujitaki et al., 1981), however the diphospho form has only been reported in chemically phosphorylated proteins. Unlike the phosphoester phosphoamino acids, all forms of phosphohistidine are unstable in acidic conditions, which has made the discovery and analysis of this type of phosphorylation technically challenging and the identification of novel proteins carrying a stable phosphohistidine are rare events (Lott et al., 2006). Nevertheless, by the use of special settings in tandem mass spectrometry (Kleinnijenhuis et al., 2007) and the description of anti-phosphohistidine antibodies (Kee and Muir, 2012; Kee et al., 2013), the detection of more proteins specifically phosphorylated on histidine residues appears more likely in the future.


Alterations in reversible protein histidine phosphorylation as intracellular signals in cardiovascular disease.

Wieland T, Attwood PV - Front Pharmacol (2015)

Structures of the three forms of phosphohistidine: (A) 1-phosphohistidine; (B) 3-phosphohistidine; (C) 1,3-diphosphohistidine.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543942&req=5

Figure 1: Structures of the three forms of phosphohistidine: (A) 1-phosphohistidine; (B) 3-phosphohistidine; (C) 1,3-diphosphohistidine.
Mentions: Phosphohistidine has a number of attributes that make it different from the phosphoester phosphoamino acids. The phosphoryl group is bonded to the imidazole ring of the amino acid via a phosphoramidate bond. Since the imidazole ring contains two nitrogens, there are three forms of phosphohistidine, 1- or 3-phosphohistidine or 1,3-diphosphohistidine (see Figure 1). The two forms of monophosphohistidine are both known to occur in cellular proteins (Walinder, 1969b; Chen et al., 1977; Fujitaki et al., 1981), however the diphospho form has only been reported in chemically phosphorylated proteins. Unlike the phosphoester phosphoamino acids, all forms of phosphohistidine are unstable in acidic conditions, which has made the discovery and analysis of this type of phosphorylation technically challenging and the identification of novel proteins carrying a stable phosphohistidine are rare events (Lott et al., 2006). Nevertheless, by the use of special settings in tandem mass spectrometry (Kleinnijenhuis et al., 2007) and the description of anti-phosphohistidine antibodies (Kee and Muir, 2012; Kee et al., 2013), the detection of more proteins specifically phosphorylated on histidine residues appears more likely in the future.

Bottom Line: More recently, it has become evident that the nucleoside diphosphate kinase isoform B (NDPK-B), an ubiquitously expressed enzyme involved in nucleotide metabolism, and a highly specific phosphohistidine phosphatase (PHP) form a regulatory histidine protein kinase/phosphatase system in mammals.At least three well defined substrates of NDPK-B are known: The β-subunit of heterotrimeric G-proteins (Gβ), the intermediate conductance potassium channel SK4 and the Ca(2+) conducting TRP channel family member, TRPV5.In each of these proteins the phosphorylation of a specific histidine residue regulates cellular signal transduction or channel activity.

View Article: PubMed Central - PubMed

Affiliation: Institute for Experimental and Clinical Pharmacology and Toxicology, Mannheim Medical Faculty, Heidelberg University , Mannheim, Germany.

ABSTRACT
Reversible phosphorylation of amino acid side chains in proteins is a frequently used mechanism in cellular signal transduction and alterations of such phosphorylation patterns are very common in cardiovascular diseases. They reflect changes in the activities of the protein kinases and phosphatases involving signaling pathways. Phosphorylation of serine, threonine, and tyrosine residues has been extensively investigated in vertebrates, whereas reversible histidine phosphorylation, a well-known regulatory signal in lower organisms, has been largely neglected as it has been generally assumed that histidine phosphorylation is of minor importance in vertebrates. More recently, it has become evident that the nucleoside diphosphate kinase isoform B (NDPK-B), an ubiquitously expressed enzyme involved in nucleotide metabolism, and a highly specific phosphohistidine phosphatase (PHP) form a regulatory histidine protein kinase/phosphatase system in mammals. At least three well defined substrates of NDPK-B are known: The β-subunit of heterotrimeric G-proteins (Gβ), the intermediate conductance potassium channel SK4 and the Ca(2+) conducting TRP channel family member, TRPV5. In each of these proteins the phosphorylation of a specific histidine residue regulates cellular signal transduction or channel activity. This article will therefore summarize our current knowledge on protein histidine phosphorylation and highlight its relevance for cardiovascular physiology and pathophysiology.

No MeSH data available.


Related in: MedlinePlus