Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Studies on Phosphohistidine Phosphatase 1: What? Where? Why?
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
2012 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Phosphohistidine phosphatase 1 (PHPT1) is a small protein, consisting of 125 amino acids, that catalyzes the dephosphorylation of histidine but does not have any activity towards other phosphorylated amino acids. PHPT1 was identified in 2002, and is so far the only mammalian histidine phosphatase known, but still little is known about its physiological role. No mammalian histidine kinases have hitherto been identified.

Phosphorylation is one of the most important ways in which the structure and activity of a protein may be changed after translation. Proteins are phosphorylated on the side chain of amino acid residues. When a hydroxyl is phosphorylated the result is a phosphoester and when a nitrogen is phosphorylated the result is a phosphoamidate. Histidine may be phosphorylated on either of the two nitrogens of the imidazole ring of the side chain. The resulting phosphoamidate bond is labile and rich in energy, which makes histidine phosphorylation highly reversible and flexible. However, histidine phosphorylation is less studied than that of the phosphoesters due to the acid lability of the phosphoamidate bond.

The work described in this thesis was focused on further elucidating the physiological role of PHPT1. Amino acid residues of importance for the activity of PHPT1 were identified, and mutants with decreased phosphatase activity were produced. These mutants have been used in studies on the function of PHPT1. By using immunohistochemical methodology the localization of PHPT1 in both mouse and human tissues was determined, with mainly similar results. A general finding was that expression of PHPT1 was high in epithelial cells with short turnover time, indicating that PHPT1 may have an important role in proliferating cells. We have also developed a comparatively fast and simple screening method for determination of PHPT1 activity. Since research in this field has been hampered by the lack of efficient and practical methodology, hopefully this new method will be an asset in search of inhibitors for PHPT1, which in turn may be used for detection of the elusive mammalian histidine kinases, the finding of which may give major breakthroughs in the field.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2012. , s. 44
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 760
Emneord [en]
PHPT1, Phosphohistidine phosphatase, PHP, Assay
HSV kategori
Forskningsprogram
Medicinsk biokemi
Identifikatorer
URN: urn:nbn:se:uu:diva-171881ISBN: 978-91-554-8329-6 (tryckt)OAI: oai:DiVA.org:uu-171881DiVA, id: diva2:512904
Disputas
2012-05-16, C10:301, BMC, Husargatan 3, Uppsala, 09:15 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2012-04-25 Laget: 2012-03-28 Sist oppdatert: 2018-01-12bibliografisk kontrollert
Delarbeid
1. Mutational study of human phosphohistidine phosphatase: effect on enzymatic activity.
Åpne denne publikasjonen i ny fane eller vindu >>Mutational study of human phosphohistidine phosphatase: effect on enzymatic activity.
Vise andre…
2005 (engelsk)Inngår i: Biochem Biophys Res Commun, ISSN 0006-291X, Vol. 337, nr 3, s. 887-91Artikkel i tidsskrift (Fagfellevurdert) Published
Emneord
Amino Acid Sequence, Amino Acid Substitution, Binding Sites, Enzyme Activation, Evolution; Molecular, Humans, Molecular Sequence Data, Mutagenesis; Site-Directed, Mutation, Phosphoprotein Phosphatase/analysis/*chemistry/genetics/*metabolism, Protein Binding, Recombinant Proteins/analysis/chemistry/metabolism, Research Support; Non-U.S. Gov't, Sequence Homology; Amino Acid, Structure-Activity Relationship, Substrate Specificity
Identifikatorer
urn:nbn:se:uu:diva-80308 (URN)16219293 (PubMedID)
Tilgjengelig fra: 2006-05-05 Laget: 2006-05-05 Sist oppdatert: 2012-05-30
2. Immunohistochemical localization of phosphohistidine phosphatase PHPT1 in mouse and human tissues
Åpne denne publikasjonen i ny fane eller vindu >>Immunohistochemical localization of phosphohistidine phosphatase PHPT1 in mouse and human tissues
Vise andre…
2009 (engelsk)Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, nr 2, s. 65-72Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Protein histidine phosphorylation accounts for about 6% of the total protein phosphorylation in eukaryotic cells; still details concerning histidine phosphorylation and dephosphorylation are limited. A mammalian 14-kDa phosphohistidine phosphatase, also denominated PHPT1, was found 6 years ago that provided a new tool in the study of phosphohistidine phosphorylation. The localization of PHPT1 mRNA by Northern blot analysis revealed high expression in heart and skeletal muscle. The main object of the present study was to determine the PHPT1 expression on protein level in mouse tissues in order to get further information on the physiological role of the enzyme. Tissue samples from adult mice and 14.5-day-old mouse embryos were processed for immunostaining using a PHPT1-specific polyclonal antibody. The same antibody was also provided to the Swedish human protein atlas project (HPR) (http://www.proteinatlas.org/index.php). The results from both studies were essentially consistent with the previously reported expression of mRNA of a few human tissues. In addition, several other tissues, including testis, displayed a high protein expression. A salient result of the present investigation was the ubiquitous expression of the PHPT1 protein and its high expression in continuously dividing epithelial cells.

Emneord
Phosphohistidine phosphatase, PHPT1, PHP, phosphohistidine, dephosphorylation, HPR-project
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-119851 (URN)10.1080/03009730802642337 (DOI)000265454800001 ()19396692 (PubMedID)
Tilgjengelig fra: 2010-03-02 Laget: 2010-03-02 Sist oppdatert: 2017-12-12bibliografisk kontrollert
3.
Posten ble ikke funnet. Det kan skyldes at posten ikke lenger er tilgjengelig eller det er feil id i adressefeltet.

Open Access i DiVA

fulltext(2301 kB)1132 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 2301 kBChecksum SHA-512
fe31de93338f7f13be95f53e265b475583b81a193d90dbf8d68987eff6201769ab9d5e97c5b4eaf9c0c9b6aa705accdf3c1bee2343edfd4227921451d0207b8c
Type fulltextMimetype application/pdf
errata(79 kB)79 nedlastinger
Filinformasjon
Fil ERRATA01.pdfFilstørrelse 79 kBChecksum SHA-512
42029e9d15ec68216eb32addc94019188ef12df77116067ca4bdc048b202dff9e1a511bc7b8084f664cf976e7a4ec40ab851387abb377d301f5119d152ca586a
Type errataMimetype application/pdf
Kjøp publikasjonen >>

Søk i DiVA

Av forfatter/redaktør
Beckman Sundh, Ulla
Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 1132 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

isbn
urn-nbn

Altmetric

isbn
urn-nbn
Totalt: 1178 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf