Engineering Stem Cell Factor Ligands with Different c-Kit Agonistic Potencies.

ABSTRACT: Receptor tyrosine kinases (RTKs) are major players in signal transduction, regulating cellular activities in both normal regeneration and malignancy. Thus, many RTKs, c-Kit among them, play key roles in the function of both normal and neoplastic cells, and as such constitute attractive targets for therapeutic intervention. We thus sought to manipulate the self-association of stem cell factor (SCF), the cognate ligand of c-Kit, and hence its suboptimal affinity and activation potency for c-Kit. To this end, we used directed evolution to engineer SCF variants having different c-Kit activation potencies. Our yeast-displayed SCF mutant (SCF_M) library screens identified altered dimerization potential and increased affinity for c-Kit by specific SCF-variants. We demonstrated the delic

SUBMITTER: Tilayov T 

PROVIDER: S-EPMC7588011 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature