Cytokines are small proteins, e.g. growth hormone, that induce “signals” inside cells when they bind cell-surface receptors. Many cytokine-induced signals pass through members of the Janus kinase (JAK) family. Mutations in JAK proteins that cause blood cancers were identified a decade ago, but it has not been determined exactly how they do so. Using data collected at the Berkeley Center for Structural Biology at the Advanced Light Source and the Phenix X-ray crystallography software developed in the Physical Biosciences Division for refinement, Genentech’s Charles Eigenbrot and Patrick Lupardus led a team that determined the kinase/pseudokinase structure of JAK family member TYK2. Based on this structural information, they proposed a mechanism for how these mutations could cause blood cancers.
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