 Andrew J. Brooks

Andrew J. Brooks studies signal transduction by cytokine receptors, particularly the growth hormone receptor and its associated protein kinase JAK2. The research asks how an extracellular binding event changes the arrangement and activity of intracellular signaling machinery.^[ref]

In a 2014 study, Andrew J. Brooks and collaborators combined Förster resonance energy transfer, engineered receptor substitutions and structural modeling. They monitored the positions of JAK2-binding regions in the receptor pair. Their model connected receptor activation to a change in transmembrane geometry that separates these binding regions and relieves inhibition involving the pseudokinase region of JAK2.^[ref]

The illuminating example is a pair that already exists before activation: a change in relative orientation can matter as much as bringing two molecules together. The combination of distance-sensitive measurements, engineered perturbations and structural models tests this idea more directly than merely observing that a hormone and receptor bind. The proposed sequence is a mechanistic model assembled from complementary evidence.