NGFI-B is an inducible orphan nuclear receptor that initiates apoptosis. Growth factors such as EGF activate the MAP kinase ERK, whose activity may determine if a cell survives or undergoes apoptosis. EGF stimulation of cells leads to phosphorylation of threonine in NGFI-B. Thr-142 of NGFI-B is comprised in a consensus MAP kinase site and was identified as a preferred substrate for ERK2 (but not ERK1) in vitro. These results suggest that NGFI-B may be a molecular target for ERK2 signals and thereby a substrate for crosstalk between a growth factor survival pathway and an inducible regulator of apoptosis. (C) 2002 Elsevier Science (USA).