Transport of Exogenous Growth Factors and Cytokines to the Cytosol and to the Nucleus

In recent years a number of growth factors, cytokines, protein hormones, and other proteins have been found in the nucleus after having been added externally to cells. This review evaluates the evidence that translocation takes place and discusses possible mechanisms. As a demonstration of the principle that extracellular proteins can penetrate cellular membranes and reach the cytosol, a brief overview of the penetration mechanism of protein toxins with intracellular sites of action is given. Then problems and pitfalls in attempts to demonstrate the presence of proteins in the cytosol and in the nucleus as opposed to intracellular vesicular compartments are discussed, and some new approaches to study this are described. A detailed overview of the evidence for translocation of fibroblast growth factor, HIV-Tat, interferon-gamma, and other proteins where there is evidence for intracellular action is given, and translocation mechanisms are discussed. It is concluded that although there are many pitfalls, the bulk of the experiments indicate that certain proteins are indeed able to enter the cytosol and nucleus. Possible roles of the internalized proteins are discussed.