ABSTRACT
The protein kinase-coupled receptors of eukaryotes share a common mechanism of activation. The kinase activity is mostly intrinsic, harbored in the cytoplasmic domain of the protein, while only a few receptors associate noncovalently with a separate His kinase. These two principles—intrinsic versus associated protein kinase activity—have been preserved throughout evolution, even though during eukaryotic development the His-specific kinases were replaced by serine/threonine- and tyrosine- specific kinase activities. Moreover, phosphorylation may prolong signal transduction across the cell membrane: even when the ligand has dissociated, the receptor or the associated protein kinase, respectively, stays active until it is dephosphorylated by a cognate protein phosphatase. Depending on the receptor type, the role of the ligand is to induce or stabilize a conformational change that promotes oligomerization or stabilizes preformed oligomeric receptor complexes. Depending on the receptor type, this occurs according to two different principles: either the monomers phosphorylate each other or—rather an exception—one monomer phosphorylates the other one, which transmits the signal downstream.
