ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK

We identified a 46-kDa ERK, whose kinetics of activation was similar to tha t of ERK1 and ERK2 in most cell lines and conditions, but showed higher fol d activation in response to osmotic shock and epidermal growth factor treat ments of Ras-transformed cells. We purified and cloned this novel ERK (ERK1 b), which is an alternatively spliced form of ERK1 with a 26-amino acid ins ertion between residues 340 and 341 of ERK1. When expressed in COS7 cells, ERK1b exhibited kinetics of activation and kinase activity similar to those of ERK1. Unlike the uniform pattern of expression of ERK1 and ERK2, ERK1b was detected only in some of the tissues examined and seems to be abundant in the rat and human heart. Interestingly, in has-transformed Rat1 cells, t here was a 7-fold higher expression of ERK1b, which was also more responsiv e than ERK1 and ERK2 to various extracellular treatments. Unlike ERK1 and E RK2, ERK1b failed to interact with MEK1 as judged from its nuclear localiza tion in resting cells overexpressing ERK1b together with MEK1 or by lack of coimmunoprecipitation of the two proteins. Thus, ERK1b is a novel 46-kDa E RK isoform, which seems to be the major ERK isoform that responds to exogen ous stimulation in Ras-transformed cells probably due to its differential r egulation by MEK.