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Paralog-Specific Patterns Of Structural Disorder And Phosphorylation In The Vertebrate Sh3–Sh2–Tyrosine Kinase Protein Family, Helena G. Dos Santos, Jessica Siltberg-Liberles

Biomolecular Sciences Institute: Faculty Publications

One of the largest multigene families in Metazoa are the tyrosine kinases (TKs). These are important multifunctional proteins that have evolved as dynamic switches that perform tyrosine phosphorylation and other noncatalytic activities regulated by various allosteric mechanisms. TKs interact with each other and with other molecules, ultimately activating and inhibiting different signaling pathways. TKs are implicated in cancer and almost 30 FDA-approved TK inhibitors are available. However, specific binding is a challenge when targeting an active site that has been conserved in multiple protein paralogs for millions of years. A cassette domain (CD) containing SH3–SH2–Tyrosine Kinase domains reoccurs in vertebrate …