Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein beta gamma dimers

• Verfasst von: Wieland, Thomas [VerfasserIn]
• Titel: Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein beta gamma dimers
• Titelzusatz: consequences on G protein activation and stability
• Verf.angabe: Thomas Wieland
• E-Jahr: 2007
• Jahr: 3 January 2007
• Umfang: 11 S.
• Fussnoten: Gesehen am 24.02.2022
• Titel Quelle: Enthalten in: Naunyn-Schmiedeberg's archives of pharmacology
• Ort Quelle: Berlin : Springer, 1873
• Jahr Quelle: 2007
• Band/Heft Quelle: 374(2007), 5/6, Seite 373-383
• ISSN Quelle: 1432-1912
• DOI: doi:10.1007/s00210-006-0126-6
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adenylyl-cyclase
• Sach-SW: binding regulatory proteins
• Sach-SW: energy phosphate transfer
• Sach-SW: G beta gamma dimers
• Sach-SW: heart-failure
• Sach-SW: heterotrimeric G proteins
• Sach-SW: histidine phosphatase
• Sach-SW: human-platelet membranes
• Sach-SW: independent activation
• Sach-SW: nm23-H2
• Sach-SW: nucleoside diphosphate kinase
• Sach-SW: nucleotide exchange
• Sach-SW: phosphotransfer reactions
• Sach-SW: signal transduction
• Sach-SW: signal-transduction
• K10plus-PPN: 1793817634

Abstract

It is generally accepted that G protein coupled receptors (GPCR) activate heterotrimeric G proteins by inducing a GDP/GTP exchange at the G protein alpha subunit. In addition, the transfer of high energetic phosphate by nucleoside diphosphate kinase (NDPK) and/or the beta subunit of G proteins (G beta) can induce G protein activation. Recent evidence suggests that the NDPK isoform B (NDPK B) forms a complex with G beta gamma dimers. In this complex, NDPK B acts as a protein histidine kinase phosphorylating G beta at histidine residue 266 (His266). The high energetic phosphoamidate bond on His266 allows for a phosphate transfer specifically onto GDP and thus local formation of GTP, which binds to and thereby activates the respective G protein alpha subunit. Apparently, this process occurs independent of the classical GPCR-induced GDP/GTP exchange at least for members of the G(s) and G(i) subfamilies of heterotrimeric G proteins. By using a mutant of G beta(1) in which His266 was replaced by Leu, it was recently demonstrated that NDPK B/G beta gamma-mediated G(s) activation contributes by about 50% to basal cAMP formation and contractility in rat cardiac myocytes. Besides its apparent role in G protein activation, the complex formation of NDPK B with G beta gamma dimers might be essential for G protein stability. Depletion of either the NDPK B orthologue or G beta(1) isoforms in zebrafish embryos led to a similar phenotype displaying contractile dysfunction in the heart accompanied by a complete loss of heterotrimeric G protein expression. In conclusion, the interaction of NDKP B with G beta gamma dimers might play an important role in signal transduction, and alterations in this novel pathway might be of pathophysiological importance.