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 factor 3 (eIF3). p170 was recently cloned and little is known concerning its characteristics and subcellular localization. In this paper, we report our surprising findings that about 20% of p170 is associated with membranes while the remaining portion is located in the cytoplasm presumably in the eIF3 complex. We also find that p170 interacts with both endoplasmic reticulum and plasma membranes. The binding of p170 to membranes is through actin filaments, consistent with the fact that p170 contains a spectrin repeat motif that may be involved in actin binding. Furthermore, the cytoplasmic p170 is phosphorylated at serine and threonine residues and the phosphorylation is stimulated by serum. However, the membrane-actin-bound p170 is not phosphorylated. The results obtained in this study suggest that p170 may have other functions in addition to participating in translation initiation. Phosphorylation may play an important regulatory role in the function of p170 in translation initiation and other alternative functions.
Pincheira
R
R
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202, USA.
Chen
Q
Q
Huang
Z
Z
Zhang
J T
JT
D018435:ATP Binding Cassette Transporter, Subfamily B; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000199:Actins; D039621:Eukaryotic Initiation Factor-3; D006023:Glycoproteins; D010448:Peptide Initiation Factors