SRP408408 PRJNA902714 GSE218190 Molecular determinants of Hsp90 recognition of Src kinase revealed by deep mutational scanning Protein tyrosine kinases are involved in regulating growth and proliferation in cells and are often hyperactive in cancerous tissue. Tyrosine kinase inhibitors have been used to limit hyperactivity but become ineffective due to the appearance of resistance mutations. A common trait of hyperactive protein kinases is its strict client relationship with molecular chaperone Hsp90. However, the mechanism behind Hsp90 client kinase recognition is poorly understood. Here we measure the functional effect of thousands of single amino acid variants in the Src kinase domain to identify positions invovled in Hsp90 client recognition. Overall design: A barcoded plasmid library of Src variants was expressed in S. cerevisiae and four samples were collected during duplicate outgrowth experiments. Plasmid DNA was extracted from each sample from which barcodes were amplified and counted via Illumina sequencing. Barcodes were linked to a corresponding variant sequence using a barcode sequence map. GSE218190 pubmed 37167432