G protein βγ subunit activates Ras, Raf, and MAP kinase in HEK 293 cells

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Abstract
Using transient transfection of HEK 293 cells, we have studied the activation of Ras, c‐Raf, and MAP kinase by G protein‐coupled receptors, activated G protein α subunit (Gα), and βγ subunits (Gβγ). The expression of constitutively activated Gsα, Giα, and Gaaα did not have any effect on MAP kinase phosphorylation. In contrast, overexpression of Gβγ could stimulate the phosphorylation of MAP kinase and enhance the MEK kinase activity of c‐Raf. Coexpression of dominant negative Ras inhibited Gβγ‐induced phosphorylation of MAP kinase. Furthermore, the GTP‐bound form of Ras was increased by overexpression of Gβγ. These results strongly suggest that the Gβγ may play an important role in signaling from G protein‐coupled receptors to the MAP kinase pathway, and the activation of Ras and c‐Raf may be involved in this signaling cascade in HEK 293 cells.