An intact helical domain is required for G?14 to stimulate phospholipase C?.

ABSTRACT: Stimulation of phospholipase C? (PLC?) by the activated ?-subunit of Gq (G?q) constitutes a major signaling pathway for cellular regulation, and structural studies have recently revealed the molecular interactions between PLC? and G?q. Yet, most of the PLC?-interacting residues identified on G?q are not unique to members of the G?q family. Molecular modeling predicts that the core PLC?-interacting residues located on the switch regions of G?q are similarly positioned in G?z which does not stimulate PLC?. Using wild-type and constitutively active chimeras constructed between G?z and G?14, a member of the G?q family, we examined if the PLC?-interacting residues identified in G?q are indeed essential.Four chimeras with the core PLC?-interacting residues composed of G?z sequences were capable of binding PLC?2 and stimulating the formation of inositol trisphosphate. Surprisingly, all chimeras with a G?z N-terminal half failed to functionally associate with PLC?2, despite the fact that many of them contained the core PLC?-interacting residues from G?14. Further analyses revealed that the non-PLC?2 interacting chimeras were capable of interacting with other effector molecules such as adenylyl cyclase and tetratricopeptide repeat 1, indicating that they could adopt a GTP-bound active conformation.Collectively, our study suggests that the previously identified PLC?-interacting residues are insufficient to ensure productive interaction of G?14 with PLC?, while an intact N-terminal half of G?14 is apparently required for PLC? interaction.

SUBMITTER: Kwan DH 

PROVIDER: S-EPMC4573470 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature