Protein kinases and phosphatases that act on histidine, lysine, or arginine residues in eukaryotic proteins: A possible regulator of the mitogen-activated protein kinase cascade

Matthews, Harry R.

doi:10.1016/0163-7258(95)00020-8

Cited by 175 publications

(145 citation statements)

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“…Roles for N-linked phosphorylation in prokaryotic signal transduction functions are established, 36 but histidine or lysine phosphorylation has been less studied in eukaryotes. 37,38 Since Htr1a is a G-protein-coupled receptor, it is of interest that a G-protein b subunit is one of the few human protein for which a regulatory role of N-linked phosphorylation has been described. [39][40][41][42][43] LHPP does not share meaningful sequence homology with either of the identified human phosphoamidases, 44,45 although these also are not homologous to each other.…”

Section: Discussionmentioning

confidence: 99%

“…These transcripts are shown in Figure 4. Expression levels were categorized according to threshold cycle: very high ( < 20), high (20)(21)(22)(23)(24)(25), moderate (25)(26)(27)(28)(29)(30), low (30)(31)(32)(33)(34)(35), very low/questionable (35)(36)(37)(38)(39)(40) or not detected (no signal above background after 40 cycles). Because of the linkage and association of LHPP variants to MDD, there was particular focus on measuring expression of these transcripts in the brain (Figure 3b).…”

Section: Serotonin Receptor 1a-conditional Genetic Analysismentioning

confidence: 99%

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Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

et al. 2008

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The HTR1A À1019C > G genotype was associated with major depression in the Utah population. Linkage analysis on Utah pedigrees with strong family histories of major depression including only cases with the HTR1A À1019G allele revealed a linkage peak on chromosome 10 (maximum HLOD = 4.4). Sequencing of all known genes in the linkage region revealed disease-segregating single-nucleotide polymorphisms (SNPs) in LHPP. LHPP SNPs were also associated with major depression in both Utah and Ashkenazi populations. Consistent with the linkage evidence, LHPP associations depended on HTR1A genotype. Lhpp or a product of a collinear brain-specific transcript, therefore, may interact with Htr1a in the pathogenesis of major depression.

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Section: Discussionmentioning

confidence: 99%

Section: Serotonin Receptor 1a-conditional Genetic Analysismentioning

confidence: 99%

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

et al. 2008

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“…One is the intermediary phosphorylation of enzymes [5][6][7][8][9][10], of which nucleoside diphosphate kinase is a particularly well-studied example. The other is the reversible protein histidine phosphorylation by protein kinases and phosphatases [3,11]. An important contribution to the latter field was the purification of a yeast protein histidine kinase in 1991 [12].…”

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confidence: 99%

Identification and characterization of a mammalian 14‐kDa phosphohistidine phosphatase

Pettersson

et al. 2002

European Journal of Biochemistry

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Protein histidine phosphorylation in eukaryotes has been sparsely studied compared to protein serine/threonine and tyrosine phosphorylation. In an attempt to rectify this by probing porcine liver cytosol with the phosphohistidinecontaining peptide succinyl-Ala-His(P)-Pro-Phe-p-nitroanilide (phosphopeptide I), we observed a phosphatase activity that was insensitive towards okadaic acid and EDTA. This suggested the existence of a phosphohistidine phosphatase different from protein phosphatase 1, 2A and 2C. A 1000-fold purification to apparent homogeneity gave a 14-kDa phosphatase with a specific activity of 3 lmolAEmin )1 AEmg )1 at pH 7.5 with 7 lM phosphopeptide I as substrate. Partial amino-acid sequence determination of the purified porcine enzyme by MS revealed similarity with a human sequence representing a human chromosome 9 gene of hitherto unknown function. Molecular cloning from a human embryonic kidney cell cDNAlibrary followed by expression and purification, yielded a protein with a molecular mass of 13 700 Da, and an EDTA-insensitive phosphohistidine phosphatase activity of 9 lmolAEmin )1 AEmg )1 towards phosphopeptide I. No detectable activity was obtained towards a set of phosphoserine-, phosphothreonine-, and phosphotyrosine peptides. Northern blot analysis indicated that the human phosphohistidine phosphatase mRNA was present preferentially in heart and skeletal muscle. These results provide a new tool for studying eukaryotic histidine phosphorylation/dephosphorylation.Keywords: dephosphorylation; N-phosphorylation; phosphoamidase; phosphopeptide; protein histidine phosphatase.Boyer and coworkers detected protein-bound phosphohistidine in rat-liver mitochondrial succinyl-CoA synthetase almost 40 years ago [1,2]. Despite the long time interval and the fact that phosphohistidine represents a substantial fraction of eukaryotic protein-bound phosphate [3], only a few phosphohistidine-containing proteins have been detected compared to the large number of eukaryotic proteins phosphorylated on serine, threonine and tyrosine residues. One reason for this difference may be that the N-bound phosphate of phosphohistidine easily escapes detection by common analytical procedures, due to its lability under acidic conditions, e.g. during fixation and staining of gels after SDS/PAGE [4].The studies on eukaryotic protein histidine phosphorylation and dephosphorylation have dealt with essentially two aspects. One is the intermediary phosphorylation of enzymes [5][6][7][8][9][10], of which nucleoside diphosphate kinase is a particularly well-studied example. The other is the reversible protein histidine phosphorylation by protein kinases and phosphatases [3,11]. An important contribution to the latter field was the purification of a yeast protein histidine kinase in 1991 [12]. Access to this enzyme also made possible the preparation of 32 P-labelled histone H4, which was later used as substrate in the search for phosphohistidine phosphatases. Using such an approach, the catalytic subunits of the well-studied serine/...

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“…28 In this particular case, it is not clear which isomer of pHis is formed and on which His residue. Mammalian pHis phosphatases, which have been characterized include: protein pHis phosphatase 1 (PHPT1); 17,[29][30][31][32][33][34][35] Lys/His phosphatase (LHPPase); 36,37 Ser Thr protein phosphatases (PP1/2 A/2C); 38,39 T-cell ubiquitin ligand-2 (TULA-2); 40,41 and the recently reported phosphoglycerate mutase-5 (PGAM5). 42 In addition, pHis phosphatase activity has been reported in rat tissue extracts but these have not been fully characterized.…”

mentioning

confidence: 99%

“…42 In addition, pHis phosphatase activity has been reported in rat tissue extracts but these have not been fully characterized. [43][44][45][46] Not only is His phosphorylation predicted to be prevalent in eukaryotic proteins, 38 it has also been associated with important mammalian cellular processes. For example, pHis has been shown to be present in heteromeric G proteins (GNB1), which are involved in G protein signalling, 15,47,48 KCa3.1 potassium channel, which is involved in ion conductance, 18,49 ATP-citrate lyase (ACLY), which is involved in cell metabolism, 9 histone H4, which is involved in chromatin biology, 21,22,28 transient receptor potentialvanilloid-5 (TRPV5), which regulates urinary Ca 2+ excretion, 17 and phosphoglycerate mutase 1 (PGAM1), which is involved in glycolysis.…”

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confidence: 99%

Advances in development of new tools for the study of phosphohistidine

Makwana

Muimo

Jackson

2018

Laboratory Investigation

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Protein phosphorylation is an important post-translational modification that is an integral part of cellular function. The O-phosphorylated amino-acid residues, such as phosphoserine (pSer), phosphothreonine (pThr) and phosphotyrosine (pTyr), have dominated the literature while the acid labile N-linked phosphorylated amino acids, such as phosphohistidine (pHis), have largely been historically overlooked because of the acidic conditions routinely used in amino-acid detection and analysis. This review highlights some misinterpretations that have arisen in the existing literature, pinpoints outstanding questions and potential future directions to clarify the role of pHis in mammalian signalling systems. Particular emphasis is placed on pHis isomerization and the hybrid functionality for both pHis and pTyr of the proposed τ-pHis analogue bearing the triazole residue.

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Protein kinases and phosphatases that act on histidine, lysine, or arginine residues in eukaryotic proteins: A possible regulator of the mitogen-activated protein kinase cascade

Cited by 175 publications

References 140 publications

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

Identification and characterization of a mammalian 14‐kDa phosphohistidine phosphatase

Advances in development of new tools for the study of phosphohistidine

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