Building blocks. Building blocks or modules of signaling pathways. Despite their diversity, signaling pathways often employ a set of common components (modules, motifs, building blocks) including the depicted ones. A) Receptors sense specific ligands or stimuli and change their conformation from the susceptible form Rs to the active form Ra, which transfers the signal downstream. Cells can fine-tune their excitability by (i) changing the susceptibility of receptors, e.g. switch between Rs and inactive form Ri, or (ii) by regulating the number of receptors via production or internalization and degradation. B) G proteins are heterotrimers consisting of subunits α, β, and γ. In the ground state, the α-subunit is bound to GDP. The active receptor triggers the activation of the G protein by exchanging the GDP with a GTP. The G protein dissociates into its subunits, which transmit the signal downstream by binding to other proteins and activating or inhibiting biochemical processes. The α-subunit carries the GTP. After GTP hydrolysis, which is a highly regulated process on its own, the subunits can reassociate to form the initial heterotrimeric G protein. The Regulator of G protein signaling (RGS) is involved in a larger feedback loop. C) Small G proteins switch between GDP-bound or GTP-bound forms with different activities. Conversion from the GDP state to the GTP state is catalyzed by a so-called Guanine Exchange Factor (GEF), the reverse process is facilitated by a GTPase-activation protein (GAP), which induces hydrolysis of the bound GTP . D) MAPK (mitogen activated kinase) cascades consist of three or four different proteins (the kinases) that specifically catalyze the phosphorylation of the subsequent kinases under consumption of ATP. In this case, Raf is a MAPKKK, MEK is a MAPKK, and ERK is a MAPK. The number of phosphorylation events on each level can differ. Dephosphorylation is exerted by phosphatases (denoted by PP).
Klipp and Liebermeister BMC Neuroscience 2006 7(Suppl 1):S10 doi:10.1186/1471-2202-7-S1-S10