Regulation of cell-to-cell communication by phosphorylation

Abstract

The cyclic AMP-activated protein kinase I, a serine- and threonine-phosphorylating enzyme, regulates cell-to-cell communication. Its deficiency in mutant cells is associated with deficiency of communication. The communication defect is corrected by introduction of the catalytic subunit of the enzyme into the mutant cells. Activation of the enzyme by cyclic AMP in normal cells causes an increase of communication, namely an increase of junctional permeability associated with an increase in the number of membrane particles of gap junction. This upregulation of cell-to-cell membrane channels constitutes a basic mechanism whereby cell communities set their degree of communication. The mechanism is normally put into motion by adenylate cyclase-activating hormones. The mechanism is counteracted by tyrosine-phosphorylating protein kinase (src protein), which downregulates junctional permeability, a fast and reversible effect on the channels, independent of the action of the kinase on the cytoskeleton. The two T proteins coded by the SV-40 genome cause a similar channel downregulation.