G(z) signaling: emerging divergence from G(i) signaling

Oncogene. 2001 Mar 26;20(13):1615-25. doi: 10.1038/sj.onc.1204190.


A large variety of neurotransmitters, hormones, and chemokines regulate cellular functions via cell surface receptors that are coupled to guanine nucleotide-binding regulatory proteins (G proteins) belonging to the G(i) subfamily. All members of the G(i) subfamily, with the sole exception of G(z), are substrates for the pertussis toxin ADP-ribosyl transferase. G(z) also exhibits unique biochemical and regulatory properties. Initial portrayals of the cellular functions of G(z) bear high resemblance to those of other G(i) proteins both in terms of the receptors and effectors linked to G(z). However, recent discoveries have begun to insinuate a distinct role for G(z) in cellular communication. Functional interactions of the alpha subunit of G(z) (Galpha(z)) with the NKR-P1 receptor, Galpha(z)-specific regulator of G protein signaling, p21-activated kinase, G protein-regulated inducers of neurite outgrowth, and the Eya2 transcription cofactor have been demonstrated. These findings provide possible links for G(z) to participate in cellular development, survival, proliferation, differentiation and even apoptosis. In this review, we have drawn a sketch of a signaling network with G(z) as the centerpiece. The emerging picture is one that distinguishes G(z) from other members of the G(i) subfamily.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Division
  • Cell Transformation, Neoplastic
  • GTP-Binding Protein alpha Subunits*
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Models, Biological
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction*
  • p21-Activated Kinases


  • GNAZ protein, human
  • GTP-Binding Protein alpha Subunits
  • Protein Serine-Threonine Kinases
  • p21-Activated Kinases
  • Protein Kinase C
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins