PROTECTIVE EFFECT OF THE INSULIN-LIKE-GROWTH-FACTOR-I RECEPTOR ON APOPTOSIS INDUCED BY OKADAIC ACID

Okadaic acid (OKA), a potent inhibitor of serine phosphatases at conce ntrations as low as 20-25 nM, induces apoptosis of R- mouse embryo fib roblasts, which are 3T3-like cells devoid of type 1 insulin-like growt h factor receptors (IGF-IRs), From R- cells, we have generated (by sta ble transfection) cell lines with IGF-IR numbers ranging from 0 (R- ce lls) to >10(6) receptors per cell, The wild-type IGF-IR protects R- ce lls from OKA-induced apoptosis, its protective effect being exquisitel y dependent on the number of receptors, A small increment in wild-type receptor number (from 15 x 10(3) to 22 x 10(3) receptors/cell) is suf ficient to change R--derived cells from sensitive to resistant to apop tosis, We have also studied the effect of various mutations of the IGF -IR on its ability to protect R--derived cells from OKA-induced apopto sis, Our data indicate a correlation between protection from apoptosis and the ability of the receptor to respond to insulin-like growth fac tor I with mitogenesis.