Gqα and G11α differ from other G protein α subunits in that they have unique, conserved 6 residue amino-terminal extensions. Wild-type and amino-terminal mutants of Gqα expressed in COS cells were analyzed for their ability to functionally couple with co-expressed neurokinin NK2 receptor. Wild-type, T2A and Δ2–7 Gqα were able to stimulate agonist driven phospholipase C (PLC) activity in identical manners. Other activities of these two amino-terminal mutants including aluminum fluoride stimulated PLC activity, palmitoylation, interaction with Gβγ subunits and GTPγS-induced trypsin resistance are also similar to the wild-type α subunit. This demonstrates that the NK2 receptor is able to functionally interact with the α subunit of Gq and that the first seven amino-acids of Gqα are not required for any of the α subunit functions tested. In contrast to the T2A and Δ2–7 mutants, a C9,10A Gqα mutant was not able to couple to either the NK2 receptor or PLC, as assessed by high-affinity agonist binding and activation of PLC either in intact cells or in vitro. The C9,10A protein was able to assume a GTPγS-induced trypsin-resistant conformation and partitioned primarily to the pelletable fraction in a manner similar to the wild-type protein. However, it was not labeled with [3H]palmitic acid. This suggests that blocking palmitoylation at the amino-terminus of Gqα results in a loss of functional activity which reflects an inability to interact with both the receptor and downstream signaling targets.
