Heterogeneity in the phosphorylation of human death receptors by p42(mapk/erk2)

Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibi t its ability to initiate apoptosis while preserving signaling events such as NF-(B kappa) activation. Therefore, we sought to determine if p42(mapk/e rk2) was also capable of phosphorylating additional human death receptors w ithin the TNF receptor superfamily. These studies showed that CD120a and DR 3 are significantly phosphorylated by p42(mapk/erk2) but Fas, DR4 and DR5 a re not. Additionally, we demonstrated that (i) the p42(mapk/erk2) -dependen t phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal reg ions but not the death i domains of CD120a and DR3, (iii) Ser 253 is a pref erred site of phosphorylation on CD120a, and (iv) the p42(mapk/erk2)-depend ent phosphorylation of the DRS cytoplasmic domain occurred exclusively at n on-p42/44(mapk/erk2/1) consensus sites. These findings suggest that human d eath receptors segregate into two groups along lines of phylogeny with resp ect to Ser/Thr phosphorylation by p42(mapk/erk2). (C) 2001 Academic Press.