Protein kinase C zeta Interacts with a novel binding region of Galfaq to act as a functional effector Articles uri icon


  • Sánchez-Fernández, Guzmán
  • Cabezudo, Sofía
  • Caballero, Álvaro
  • García-Hoz, Carlota
  • Tall, Gregory
  • Michnick, Stephen W.
  • Mayor, Federico
  • Ribas, Catalina

publication date

  • January 2016

start page

  • 9513

end page

  • 9525


  • 18


  • 291

International Standard Serial Number (ISSN)

  • 0021-9258


  • Heterotrimeric G proteins play an essential role in the initiation of G protein-coupled receptor (GPCR) signaling through specific interactions with a variety of cellular effectors. We have recently reported that GPCR activation promotes a direct interaction between Galfaq and protein kinase C zeta (PKCzeta), leading to the stimulation of the ERK5 pathway independent of the canonical effector PLCbeta. We report herein that the activation-dependent Galfaq/PKCzeta complex involves the basic PB1-type II domain of PKCzeta and a novel interaction module in Galfaq different from the classical effector-binding site. Point mutations in this Galfaq region completely abrogate ERK5 phosphorylation, indicating that Galfaq/PKCzeta association is required for the activation of the pathway. Indeed, PKCzeta was demonstrated to directly bind ERK5 thus acting as a scaffold between Galfaq and ERK5 upon GPCR activation. The inhibition of these protein complexes by G protein-coupled receptor kinase 2, a known Galfaq modulator, led to a complete abrogation of ERK5 stimulation. Finally, we reveal that Galfaq/PKCzeta complexes link Galfaq to apoptotic cell death pathways. Our data suggest that the interaction between this novel region in Galfaq and the effector PKCzeta is a key event in Galfaq signaling.


  • signal transduction; molecular bases of disease