Distinct mode of G protein activation due to single residue substitution of active IGF-II receptor peptide Arg2410-Lys2423: evidence for stimulation acceptor region other than C-terminus of Gi alpha.

Arg2410-Lys2423 (RVGLVRGEKARKGK, peptide 14) of the human insulin-like growth factor II receptor directly activates Gi and deletion of C-terminal 4 residues from peptide 14 nullifies this activity. A study was thus made of the effects of peptides modified in the C-terminal structure. RVGLVRGEKAAKGK and RVGLVRGEKARKGA scarcely activated Gi, whereas RVGLVRGEKARAGK (peptide A5) activated Gi as much as peptide 14 did. However, peptide A5 action did not depend on Mg2+ concentration and was little affected by pertussis toxin modification of Gi alpha. Peptide A5 may thus recognize the region on Gi alpha that is distinct from the extreme C-terminus. It is consequently considered that (i) the first and the last basic residues in the C-terminal motif of peptide 14 determine the capacity for recognition of Gi and (ii) there is a region different from the C-terminus of Gi alpha, through which the C-terminal second basic residue-altered peptide 14 activates Gi in a Mg(2+)-independent manner.