STE2/SCG1-dependent inhibition of STE4-induced growth arrest by mutant STE4ΔC6 in the yeast pheromone response pathway

AbstractThe yeast pheromone response pathway involves the activation of a heterotrimeric G protein composed by SCGI (α) (also GPA1), STE4 (β), and STE18 (γ) subunits by the pheromone-activated receptors STE2 and STE3 in a and α cells, respectively. Upon exchange of bound GDP for GTP in the SCG1 subunit, the release of STE4/STE18 dimer occurs which, in turn causes activation of downstream effectors leading growth arrest and mating competence. Over-expression of STE4 also leads to growth arrest in a STE18 dependent manner. Removal of 6 amino acids from the C-terminus of STE4 rendered a subunit incapable of downstream signalling but still able to interact with STE18. This ΔC6 mutant acts as a dominant negative because it blocks the growth arresting effect obtained by over-expression of STE4. The inhibitory effect of STE4ΔC6 is dependent on the presence of the SCG1 subunit in a STE2 but not ste2 background. Inhibition of the growth arresting effect of STE4 by the ΔC6 mutant is not due to competition at the effector site, but rather involves an intrinsic activity of STE2 that is dependent on SCG1