C-terminal mutation of G protein beta subunit affects differentially extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways in human embryonal kidney 293 cells

G protein beta and gamma subunits (G beta and G gamma) form a complex that is involved in various signaling pathways. We reported that the C-terminal 10 amino acids of G beta are required for association with G gamma (Yamauchi, J., Kaziro, Y., and Itoh, H. (1995) Biochem. Biophys. Res. Commun., 214, 694-700). To evaluate further the significance of the G-terminal region of G beta in the formation of a G beta gamma complex and its signal transduction, we constructed several C-terminal mutants and expressed them in human embryonal kidney 293 cells, The mutant lacking the C-terminal 2 amino acids (Delta C2) failed to associate with G gamma, whereas deletion of the C-terminal amino acid (Delta C1), replacement of Trp at -2 position by Ala (W339A), and addition of six histidines ((His)(6)) at the G terminus did not affect the association with G gamma. We also studied the effect of these mutations on the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). Go-expression of the Delta C2 or (His), mutant with Gy did not activate MAPK/ERK at all, whereas the Delta C1 or W339A mutant showed the MAPK/ERK activation. The JNK/SAPK activity was stimulated by the W339A, Delta C2, or (His), mutant, but not by the Delta C1 mutant, These results suggest that the C-terminal region of GP participates differentially in the signaling for MAPK/ERK and JNW/SAPK activations in mammalian cells.