V. Cottin et al., Phosphorylation of the tumor necrosis factor receptor CD120a (p55) recruits Bcl-2 and protects against apoptosis, J BIOL CHEM, 276(20), 2001, pp. 17252-17260
Ligation of the tumor necrosis factor cu receptor CD120a initiates response
s as diverse as apoptosis and the expression of NF-KB-dependent pro-surviva
l genes. How these opposing responses are controlled remains poorly underst
ood. Here we demonstrate that phosphorylation by p42(mapk/erk2) inhibits th
e apoptotic activity of CD120a while preserving its ability to activate NF-
KB. Phosphorylated CD120a is re-localized from the Golgi complex to tubular
structures of the endoplasmic reticulum wherein it recruits Bcl-2. Antisen
se-mediated down-regulation of Bel-2 antagonized the localization of CD120a
to tubular structures and reversed the protection from apoptosis conferred
by receptor phosphorylation. We propose that phosphorylation of CD120a rep
resents a novel, Bcl-2-dependent mechanism by which the apoptotic activity
of the receptor may be regulated. Thus, oncogenic activation of p42(mapk/er
k2) may serve to inhibit the apoptotic activity of this death receptor whil
e preserving NF-KB-dependent responses and may thus indirectly contribute t
o a failure to eliminate cells bearing oncogenes of the Ras-Raf-MEK-p42(map
k/erk2) pathway.