Cross-talk between signaling cascades

Signaling cascades communicate and integrate extracellular signaling cues spatially and temporally via formation of defined protein-protein interactions. Scientists from the Institute of Biochemistry in Innsbruck discovered a unique mechanism which is based on binary protein-protein interactions and which explains cross talk between critically regulated signaling cascades.
Image: Schematic representation of signaling cross talk: Circles specify proteins from two signaling cascades/networks. New physical interaction of the bait:prey proteins is indicated.

Higher eukaryotic cells developed sophisticated mechanisms to respond to altering environmental conditions. Extracellular cues (e.g. light or hormones) are sensed by membrane-localized receptors and are transmitted into distinct compartments of the cell through a relay of signaling events. Such intracellular signal cascades are based on defined protein-protein interactions. The participating proteins, like kinases, GTPases and the components of the ubiquitin machinery, are mandatory for exact temporal and spatial signal processing within converging signaling cascades. Deregulation of enzyme activities und interacting proteins can lead or contribute to the etiology of diseases, such as cancer.

Dynamic cross-talk

Verena Bachmann and Eduard Stefan, scientists from the Institute of Biochemistry and the Center for Molecular Biosciences Innsbruck (CMBI), identified a unique mechanism how the second messenger molecule cAMP (cyclic adenosine-monophosphate) participates in activating the Ras-Raf-Erk cascade. The biochemists unveiled that the dynamic protein-protein interaction of the GTPase Rac with two critically controlled kinases is involved in enhancing activities of the decisively regulated Ras-Raf-Erk cascade. Mutations in some of the components of this signaling cascade contribute to the origin and/or propagation of cancer. Consequently research efforts aim to identify ways and targets to modulate aberrant Ras-Raf-Erk signaling. The results of their study have been published in the American Journal: Proceedings of the National Academy of Sciences (PNAS).

In addition Bachmann und Stefan have been involved in a second study. They contributed to the identification of a protein complex which seems to be involved in the genesis of primary brain tumors (glioblastoma). This work has been published at the same time in Nature Communications.

Both projects have been funded by the Austrian Science Fund (FWF).