Cellular signaling, amino acids

Helical cytokines are secreted proteins that function as intracellular messengers. The information content contained on their a-helical scaffolds is decoded by extracellular high-fidelity interactions with cell surface receptor chains that initiate intracellular signaling cascades leading to diverse cellular functions. Amino acid sequence analysis of the extracellular cytokine binding domains revealed two distinct receptor subclasses, class-1 and class-2 (Bazan, 1990a,b). The a-helical cytokines were subsequently defined based on the class of receptor (class 1 or class 2) they... 

The ankyrin repeat motif is one of the most common protein-protein interaction domains. Ankyrin repeats are modules of about 33 amino acids repeated in tandem. They are found in a large number of proteins with diverse cellular functions such as transcriptional regulators, signal transducers, cell-cycle regulators, and cytoskeletal proteins. 

The IFN-y receptor (the type II receptor) displays a more limited cellular distribution than that of the type I receptors (Table 8.5). This receptor is a transmembrane glycoprotein of molecular mass 50 kDa, which appears to function as a homodimer. The extracellular IFN-y binding region consists of approximately 200 amino acid residues folded into two homologous domains. Initiation of signal transduction also requires the presence of a second transmembrane glycoprotein known as AF-1 (accessory factor 1), which associates with the extracellular region of the receptor. 

Phosphorylation of serine, threonine, or tyrosine residues by protein kinases, and their dephosphorylation by protein phosphatases, are critical mechanisms by which information-relaying signals are transduced in eukaryotic cells. Although protein kinases are by no means an eukaryotic invention (see Leonard et al., 1998 for details), the large numbers of protein kinases in eukaryotes (118 in. S . cerevisiae and 435 in C. elegans (Chervitz et al., 1998)) reflect their importance in a multitude of diverse cellular processes. Eukaryotes have evolved signaling pathways that exploit the dual state of an amino acid, dependent on its state of phosphorylation, both as a signaling mechanism and as a means of colocalization of molecules within multimolecular complexes. 

The members of the protein kinase C family are central signal proteins and as such, are involved in the regulation of a multitude of cellular processes. A problem in the identification of substrates of protein kinase C is its low substrate specificity which often cannot be differentiated from that of protein kinase A, particularly in in vitro experiments. The consensus sequence of the phosphorylation sites in substrate proteins are similar to those of protein kinase A, in that basic amino acids are required in the neighborhood of the Ser/Thr residue to be phosphorylated. The following consensus sequences may be formulated for phosphorylation by protein kinase C ( = phosphorylation site) S /T XK/R K/RXXS /T K/RXXS /T XK/R K/RXS /T K/RXS /T XK/R (Pearson and Kemp, 1991). 

---