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♦ See referenced article, J. Biol. Chem. 2015, 290, 10018–10036
Researchers in the area of signal transduction want to make quantitative measurements of receptor activation and the subsequent downstream events and their effects on cellular physiology. In this Paper of the Week, a team led by Adrian Whitty at Boston University analyzed the activation of a receptor tyrosine kinase called RET. The kinase is involved in the development of the kidneys and the nervous system during embryogenesis; in the adult, it maintains certain neuronal cells. The investigators used quantitative immunoassays to analyze how the RET receptor activates two downstream pathways, ERK and Akt, which are important for cell survival, growth, and differentiation. Whitty and colleagues established that RET most efficiently activated the two pathways when the concentration of its ligand, ART, was at low and functionally relevant levels. “Our results illustrate that measurements using high, super-physiological growth factor levels can be misleading about quantitative features of receptor signaling,” say the authors.