In order to probe intracellular signaling based on interactions of thousand
s of proteins expressed in the living cell, new methods of noninvasive deli
very of functional peptides and proteins to cells have been developed. Thes
e include cellular import of peptides and proteins based on the cell-membra
ne-permeable properties of the hydrophobic region of a signal peptide seque
nce. The prototypical cell-permeable SN50 peptide, which contains the nucle
ar localization signal sequence of NK-kappa B p50, has been applied in mult
iple cell types to block nuclear import of this and other transcription fac
tors. Further developments, including site-specific ligation of bipartite i
mport peptides and production of import-competent recombinant proteins, pro
vide the means for easy and rapid delivery of peptides and proteins to a wi
de spectrum of cells in order to regulate intracellular pathways involved i
n adhesion, signaling and trafficking to the nucleus.