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Superinduction by cycloheximide of mitogen‐induced secreted proteins produced by Balb/c 3T3 cells
Author(s) -
Hamilton Richard T.,
NilsenHamilton Marit,
Adams Greg
Publication year - 1985
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041230208
Subject(s) - cycloheximide , dna synthesis , epidermal growth factor , protein biosynthesis , biology , autocrine signalling , fibroblast growth factor , growth factor , lymphokine , protein synthesis inhibitor , 3t3 cells , microbiology and biotechnology , endocrinology , cell culture , biochemistry , dna , in vitro , receptor , transfection , genetics
We describe here some of the characteristics of the regulation of a group of secretory proteins whose secreted levels rise within 2–4 h of adding fibroblast growth factor (FGF), epidermal growth factor (EGF), or serum to quiescent Balb/c 3T3 cells. The levels of these secretory proteins are regulated similarly to the interferons. When cycloheximide is present during the induction period, the amounts of [ 35 S]methionine incorporated into five of these proteins that we have called “superinducible proteins” (SIPs) is increased 2–5 fold. Superinduction of the SIPs is seen also in response to polyribol‐polyriboC, the classical inducer of interferons. None of the SIPs, however, are immunoprecipitated by anti‐β‐interferon antibody. Induction and superinduction of the SIPs is inhibited by actinomycin D. Superinduction occurs at concentrations of cycloheximide that inhibit protein synthesis by at least 85%. The SIPs are not major intracellular proteins; they are barely detectible in cellular peptide growth factor to stimulate DNA synthesis; EGF, FGF, and serum induce the SIPs, whereas insulin does not, and insulin alone weakly stimulates DNA synthesis in these cells. Because FGF, EGF, and serum cause the SIPs to be produced at concentrations of cycloheximide that inhibite 85% of bulk protein and DNA synthesis, it follows that the SIPs are produced directly from the action of the growth factor and not as a consequence of increased growth. Although probably not interferons, in analogy to the lymphokines, the SIPs could be a set of autocrine or paracrine factors that rapidly convey the growth of differentiation signal between cells.