FIG. 5.

Gap junctional modulation of signal transduction. Signal transduction begins with a cell receptor binding to a ligand within an asymmetric tissue. Varying arrangements of cell types, as well as impermeable barriers to ligands created by tight junctions significantly contributes to tissue asymmetry, thus limiting the cell types that interact with soluble extracellular ligands. We hypothesize that these active ligand- receptor complexes recruit signal transduction proteins that generate small molecular weight (≤1000 Da) cofactors such as H₂O₂ produced in response to extracellular signals. Transient closure of gap junction channels during mitogenic initiation are, thus, needed to prevent a low molecular weight cofactor (i.e., H₂O₂) from diluting through the tissue to subthreshold levels needed for the activation of signal transduction pathways such as MAPK.