The role of Nt-modifications for the fate of non-receptor kinases
Non-receptor tyrosine kinases of the SRC family (SFKs) are key regulators of essential cellular processes, including growth, differentiation, survival, and migration. These kinases transmit extracellular signals into the cellular nucleus via phospho-tyrosine signaling and play a critical roles in cancer progression, immune responses, and cellular communication.
SFKs undergo co-translational Nt-myristoylation (Nt-myr) at a glycine residue after cleavage of the initiator methionine by methionine aminopeptidases (MetAPs). Nt-myr anchors SFKs to the plasma membrane, a process essential for their function. In some cases, Nt-myristoylation is omitted and two different N-degron pathways are able to recognize and degrade the un- or improperly modified glycine to ensure protein quality control. We are using different cellular and biochemical assays, along with quantitative mass spectrometry, to investigate these pathways and exploit them as potential therapeutic targets.