CELLULAR IMPORT OF FUNCTIONAL PEPTIDES TO BLOCK INTRACELLULAR SIGNALING

During the past few years, new approaches to the delivery of functiona l peptides to cells have been developed to probe intracellular protein -protein interactions. These approaches include a method based on the cell membrane permeability properties of the hydrophobic region of the signal sequence. This method provides easy and rapid delivery of func tional peptides to a wide spectrum of cells involved in inflammatory a nd immune reactions (monocytes, endothelial cells, and T lymphocytes) as well as to NIH 3T3 cells and erythroleukemia HEL cells. The method has been applied to block signaling to the nucleus by transcription fa ctors nuclear factor-kappa B, AP-1,and nuclear factor of activated T c ells, and to inhibit cell adhesion regulated by the cytoplasmic tails of integrins beta(3) and beta(1). New methods of peptide delivery prov ide direct access to intracellular proteins involved in adhesion, sign aling, and trafficking to the nucleus.