IGF-1R

Prager et al. (1992) showed that a mutant human IGF-I receptor interfered with the expected suppression of growth hormone in cultured rat pituitary cells, thus demonstrating a dominant-negative phenotype. (The 'dominant-negative' concept was first clearly articulated by Herskowitz (1987). He recognized 2 classes. The first class comprises multimeric proteins dependent on oligomerization for activity; the presence in a multimer of a mutant subunit with intact binding but altered catalytic domains can abrogate the function of the entire multimer. The second class involves monomeric proteins, in which dominant-negative mutations can occur if substrate is limiting; a mutant able to bind the substrate but not metabolize it would have this effect.)