Two subcellular localizations of eIF3 p170 and its interaction with membrane-bound microfilaments: implications for alternative functions of p170

We previously identified a 170-kDa protein (p170) highly expressed in lung cancers as the major subunit of the eukaryotic translation initiation facto r 3 (eIF3). p170 was recently cloned and lit tie is known concerning ifs ch aracteristics and subcellular localization. In this paper, we report our su rprising findings that about 20% of p170 is associated with membranes while the remaining portion is located in the cytoplasm presumably in the eIF3 c omplex. We also find that p170 interacts with both endoplasmic reticulum an d plasma membranes. The binding of p170 to membranes is through actin filam ents, consistent with the bet that p170 contains a spectrin repeat moth tha t may be involved in actin binding. Furthermore, the cytoplasmic p170 is ph osphorylated at serine and threonine residues and the phosphorylation is st imulated by serum. However, the membrane-actin-bound p170 is not phosphoryl ated. The results obtained in this study suggest that p170 may have other f unctions in addition to participating in translation initiation, Phosphoryl ation may play an important regulatory role in the function of p170 in tran slation initiation and other alternative functions.