THE TIS GENES, PRIMARY RESPONSE GENES INDUCED BY GROWTH-FACTORS AND TUMOR PROMOTERS IN 3T3 CELLS

A wide variety of cellular responses to extracellular ligands share a common generic pathway. (1) A hydrophilic ligand (a growth factor, hormone, neurotransmitter, morphogen, or antigen) binds to a transmembrane receptor present on the responding cell. (2) An intracellular signal is generated by the bound receptor, as a consequence of this ligand-receptor interaction. (3) Signal-transduction mechanisms within the cytoplasm activate intracellular protein kinases. (4) Latent transcription factors are activated by phosphorylation and/or dephosphorylation, initiating the transcription of previously quiescent genes. (5) The new transcripts are translated into proteins whose functions alter the biological properties of the cell. Stimulation of cell division in response to growth factors is therefore, a special case of a generalized biological mechanism by which extracellular ligands elicit cellular responses as a consequence of ligand-induced gene expression. The roles of some of the primary response genes, such as tis21/pc3 and tis7/pc4, remain obscure, despite the description of their encoded proteins and gene structure. To address problems in the context of the mitogenic response, ones isolated cDNAs for a group of genes induced in Swiss 3T3 cells by the mitogen and tumor promoter tetradecanoyl phorbol acetate (TPA, or simply, phorbol). © 1994, Academic Press Inc.