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A combination of genetic and pharmacological approaches using mouse leukemia models show that STAT5 phosphorylation is one of the major drivers of the proliferation of Philadelphia chromosome–positive (BCR-ABL-positive or Ph+) chronic myeloid leukemia. Once BCR-ABL expression has been established, JAK2 is required only for lymphoid cell transformation, not for the maintenance of the lymphoid or myeloid leukemia.
Metal ions are frequently used in enzyme catalysis. The extension of computational methods to metalloenzyme redesign opens up new ways to construct enzymes with new functions.
20(S)-hydroxycholesterol, a naturally occurring oxysterol, activates the Hedgehog signaling pathway by directly binding an allosteric site on Smoothened.
Patch-clamp fluorometry measurements of cAMP binding and channel opening combined with global kinetic fitting revealed that ligand binding to the tetrameric hyperpolarization-activated cyclic nucleotide–gated channel is favored at the second and fourth binding events.
Mucopolysaccharidoses are inherited disorders in which inactivation of lysosomal enzymes results in accumulation of glycosaminoglycans within cells, causing tissue and organ dysfunction. A method to determine the unique end structures of the accumulated glycosaminoglycans offers a new way for diagnosis.
