STRUCTURE, MAPPING, AND EXPRESSION OF ERP, A GROWTH FACTOR-INDUCIBLE GENE ENCODING A NONTRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE, AND EFFECT OF ERP ON CELL-GROWTH

We have characterized a growth factor-inducible gene, erp, and demonst rated that it encodes a 367-amino-acid nontransmembrane tyrosine phosp hatase protein with significant similarity to the vaccinia virus HI pr otein. Immunoprecipitation analyses show that the erp protein, ERP, is rapidly induced following serum stimulation of quiescent fibroblasts. ERP has been expressed as a fusion protein with glutathione S-transfe rase and shown to have tyrosine as well as serine protein phosphatase activity. The enzymatic activity of ERP depends on the presence of red ucing agents such as dithiothreitol, and its tyrosine phosphatase acti vity is inhibited by sodium vanadate, a potent inhibitor of protein ty rosine phosphatases. The number of stable NIH 3T3 clones obtained afte r transfection with a vector expressing the complete ERP protein is re duced more than 90% compared with that after transfection with a vecto r expressing a mutated inactive ERP protein. The remaining ERP-express ing clones present a significant increase in the proportion of bi- and multinucleated cells and a decrease in proliferation rate. Studies on the genomic structure reveal that the erp transcription unit is 2.8 k bp long and split into four exons. The erp gene maps to the 17A2-17C r egion of the murine genome. Our results demonstrate that the protein p roduct of the immediate-early gene erp has a negative effect on cell p roliferation.