The long-term objective of this research program is to investigate the role of junctional cell-to-cell communication in growth control and the role of this communication in the etiology of cancer. In the present project, it will be investigated whether the growth of certain communication-deficient transformed cells can be corrected my manipulating the genes encoding the protein of the cell-cell membrane channels, the intercellular conduits of this communication; and, conversely, whether transformation can be induced by mutant genes for this protein. The role of protein kinase C in the regulation of communication and growth will be investigated. By use of mutant genes encoding kinases of enhanced enzyme activity, a correlated study will be undertaken on the kinase effects on communication, on the state of phosphorylation of the channel protein, and on growth. The main experimental approaches involve construction of recombinant DNAs, standard DNA and RNA analyses, immunoblottings, probings of junctional permeability with microinjected fluorescent tracers, analyses of protein phosphorylation including phosphoaminoacid analysis, and assays of cellular growth.
|Zimmerman, A L; Rose, B (1985) Permeability properties of cell-to-cell channels: kinetics of fluorescent tracer diffusion through a cell junction. J Membr Biol 84:269-83|