Cells can react to environmental changes by transduction of extracellular signals, to produce intracellular responses. Membrane-impermeable signal molecules are recognized by receptors, which are localized on the plasma membrane of the cell. Binding of a ligand can result in the stimulation of an intrinsic enzymatic activity of its receptor or the modulation of a transducing protein. The modulation of one or more intracellular transducing proteins can finally lead to the activation or inhibition of a so-called 'effector protein'. In many instances, this also results in altered gene expression. Phosphorylation by protein kinases is one of the most common and important regulatory mechanisms in signal transmission. This review discusses the non-channel transmembrane receptors and their downstream signaling, with special focus on the role of protein kinases.