scaffold proteins

Scaffold proteins either hold protein kinases in a latent state close to their activating cell-surface receptors, or facilitate flow of activation from one kinase to the next kinase in a signaling cascade.

The A kinase anchoring proteins (AKAPs) are prototypical scaffold proteins that organize the protein kinases and phosphatases that regulate serine/threonine phosphorylation: 'Multiprotein signaling networks create focal points of enzyme activity that disseminate the intracellular action of many hormones and neurotransmitters. Accordingly, the spatio-temporal activation of protein kinases and phosphatases is an important factor in controlling where and when phosphorylation events occur. Anchoring proteins provide a molecular framework that orients these enzymes towards selected substrates. A-kinase anchoring proteins (AKAPs) are signal-organizing molecules that compartmentalize the cAMP dependent protein kinase, phosphodiesterases, and a variety of enzymes that are regulated by second-messengers.'[s].

In an example of scaffold mediated assembly of signaling pathways, Jip1 has separate binding sites for Jnk, and for the upstream kinases MKK7 (MAPKK), MLK3 (MAPK), and HPK1, enabling Jip1 to act as a scaffold for the mammalian Jnk MAPK cascade. Jip1 also possesses SH3 and PTB domains that can tether the complex to additional proteins participating in upstream activation or localization. B

ERK MAPK docks to target proteins and phosphorylates the substrate, Rsk1.

The regulatory cyclin A subunit of CDK2 binds substrates with a conserved RXL motif, such as p107.

The AKAP protein Yotiao binds the NMDA receptor, inactive PKA, and active PP1. Thus, Yotiao brings together components that repress resting NMDA receptor and enhance channel activation.[s]