Reversible histidine phosphorylation in mammalian cells: a teeter-totter formed by nucleoside diphosphate kinase and protein histidine phosphatase 1. 2010

Thomas Wieland, and Hans-Jörg Hippe, and Katrin Ludwig, and Xiao-Bo Zhou, and Michael Korth, and Susanne Klumpp
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.

Regulation of protein phosphorylation by kinases and phosphatases is involved in many signaling pathways in mammalian cells. In contrast to prokaryotes and lower eukaryotes a role for the reversible phosphorylation of histidine residues is just emerging. The β subunit of heterotrimeric G proteins, the metabolic enzyme adenosine 5'-triphosphate-citrate lyase (ACL), and the Ca2+-activated K+ channel KCa3.1 have been identified as targets for nucleoside diphosphate kinase (NDPK) acting as protein histidine kinase and the so far only identified mammalian protein histidine phosphatase (PHPT-1). Herein, we describe the analysis of the phosphorylation and dephosphorylation of histidine residues by NDPK and PHPT-1. In addition, experimental protocols for studying the consequences of heterotrimeric G protein activation via NDPK/Gβγ mediated phosphorelay, the regulation of ACL activity and of KCa3.1 conductivity by histidine phosphorylation will be presented.

UI MeSH Term Description Entries
D009701 Nucleoside-Diphosphate Kinase An enzyme that is found in mitochondria and in the soluble cytoplasm of cells. It catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside diphosphate, e.g., UDP, to form ADP and UTP. Many nucleoside diphosphates can act as acceptor, while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.6. Deoxynucleoside Diphosphate Kinases,GDP Kinase,Nucleoside Diphosphokinases,Nucleoside-Diphosphate Kinases,Diphosphate Kinases, Deoxynucleoside,Diphosphokinases, Nucleoside,Kinase, GDP,Kinase, Nucleoside-Diphosphate,Kinases, Deoxynucleoside Diphosphate,Kinases, Nucleoside-Diphosphate,Nucleoside Diphosphate Kinase,Nucleoside Diphosphate Kinases
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D054645 Protein Phosphatase 1 A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions. PP1c Enzyme,Phosphoprotein Phosphatase-1 delta,Phosphoprotein Phosphatase-1 gamma 1,Protein Phosphatase 1, Catalytic Subunit,Protein Phosphatase 1, Catalytic Subunit, alpha Isoform,Protein Phosphatase 1, Catalytic Subunit, beta Isoform,Protein Phosphatase 1, Catalytic Subunit, delta Isoform,Protein Phosphatase 1, Catalytic Subunit, gamma Isoform,Protein Phosphatase 1, Catalytic Subunit, gamma1 Isoform,Protein Phosphatase 1, Catalytic Subunit, gamma2 Isoform,Protein Phosphatase 1, Inhibitory Subunit,Protein Phosphatase 1, Regulatory Subunit,Protein Phosphatase 1C,Protein Phosphatase 1C gamma,Protein Phosphatase 1gamma,Protein Phosphatase-1,Protein Phosphatase-1 alpha,Protein Phosphatase-1 gamma 2,Protein Phosphatase-1G,Protein Serine-Threonine Phosphatase 1 beta,Protein-Serine-Threonine Phosphatase 1 beta,Type 1 Serine Threonine Protein Phosphatase,Phosphatase-1 delta, Phosphoprotein,Phosphoprotein Phosphatase 1 delta,Phosphoprotein Phosphatase 1 gamma 1,Protein Phosphatase 1 alpha,Protein Phosphatase 1 gamma 2,Protein Phosphatase 1G,Protein Serine Threonine Phosphatase 1 beta

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