Building an understanding of scaffold protein in cell signaling

Intricate, exquisitely coordinated networks of cell-surface and intracellular proteins work together to relay signals received from outside the cell to the nucleus, regulating cell fate and activity. Both spatial and temporal precision of these signaling cascades are integral to elicit the required cellular response.

A study published in Nature last week outlined attempts by scientists to understand the role of scaffold protein in cell signaling. The researchers, including Mohamed Soliman of Cairo University, considered the function of Receptor Tyrosine Kinase (RTK) to try to understand why it is a necessary mediator in this process.

Upon activation, RTK recruits and phosphorylates the intracellular scaffold protein Shc1, which in turn binds downstream signaling proteins. Transduction of the signal culminates in altered gene expression, which leads to an array of potential cell fates.

The researchers first mapped all possible interactions between Shc1 and other cellular proteins and found 23 new Shc1-interacting proteins involved in various cellular processes. They then analyzed which proteins were bound to Shc1 at different stages following activation of RTK. The proteins involved in signaling that promotes cell division were bound early in the process, while those involved in cytoskeletal rearrangement were bound later.

This suggests that Shc1 acts as a temporal switch, which, by separating interaction pathways in time, directs the signaling output of RTK activation to either survival pathways, or cell migration pathways. The scientists suggest it may be possible to generalize that this action could describe the role of scaffold proteins in other signaling pathways.

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