TABLE 3

Summary of ric-8(md303) suppressor mutations that activate the Gαs or Gαq pathways

Allele nameAllele typeAffected proteinAmino acid changeRegion disrupted
egl-30(ce41)Gain of functionEGL-30 (Gαq) G58D11th amino acid downstream from P-loop
egl-30(ce263)Gain of functionEGL-30 (Gαq) E208KSwitch region II; third amino acid downstream from the catalytic glutamine
gsa-1(ce94)Gain of functionGSA-1 (Gαs) G45RP-loop mutation. Glycine is conserved in
   ras, where it is known as Gly12, and is
   a common site for ras gain-of-function
   mutations in human cancers
gsa-1(ce81)Gain of functionGSA-1 (Gαs) R182CSwitch region I; this is the catalytic Arg and
   also the site of cholera toxin ADP ribosylation, and this same mutation is found
   in human pituitary tumors
gsa-1(ce218)Gain of functionGSA-1 (Gαs) T185ASwitch region I; this is the catalytic Thr.
acy-1(ce2)Gain of functionACY-1 P260SNear the beginning of the C1 catalytic
   domain
acy-1(md1756)Gain of functionACY-1 A337TC1 catalytic domain. A known point of
   contact between the C1 and C2 catalytic
   domains
kin-2(ce179)Reduction of functionKIN-2 (PKA regulatory
   subunit) R92CPseudosubstrate domain; this Arg is known
   to be critical for inhibition of protein
   kinase A
kin-2(ce38)Reduction of functionKIN-2 (PKA regulatory
   subunit) G95RPseudosubstrate domain that normally
   functions to keep protein kinase A
   turned off in absence of cAMP
kin-2(ce151)Reduction of functionKIN-2 (PKA regulatory
   subunit) E137KRegion between pseudosubstrate domain
   and cAMP binding sites
  • Strongest pathway activators are underlined. See also Figure 6.