Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and caveolins: an update

Lab Invest. 2018 Feb;98(2):190-197. doi: 10.1038/labinvest.2017.103. Epub 2017 Oct 16.


Heterotrimeric G proteins are pivotal mediators of cellular signal transduction in eukaryotic cells and abnormal G-protein signaling plays an important role in numerous diseases. During the last two decades it has become evident that the activation status of heterotrimeric G proteins is both highly localized and strongly regulated by a number of factors, including a receptor-independent activation pathway of heterotrimeric G proteins that does not involve the classical GDP/GTP exchange and relies on nucleoside diphosphate kinases (NDPKs). NDPKs are NTP/NDP transphosphorylases encoded by the nme/nm23 genes that are involved in a variety of cellular events such as proliferation, migration, and apoptosis. They therefore contribute, for example, to tumor metastasis, angiogenesis, retinopathy, and heart failure. Interestingly, NDPKs are translocated and/or upregulated in human heart failure. Here we describe recent advances in the current understanding of NDPK functions and how they have an impact on local regulation of G-protein signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Caveolins / metabolism*
  • Cyclic AMP / metabolism
  • Guanosine Triphosphate / metabolism
  • Heart Failure / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Models, Biological
  • NM23 Nucleoside Diphosphate Kinases / metabolism*
  • Signal Transduction*


  • Caveolins
  • NM23 Nucleoside Diphosphate Kinases
  • Guanosine Triphosphate
  • Cyclic AMP
  • Heterotrimeric GTP-Binding Proteins