B. A. Witthuhn is the first author of a 1993 study connecting the erythropoietin receptor to the protein kinase JAK2. The biological puzzle was how erythropoietin could stimulate tyrosine phosphorylation through a receptor that lacks its own kinase protein domain. The experiments showed that JAK2 physically associates with an intracellular region of the erythropoietin receptor.[ref]
Adding erythropoietin induced JAK2 tyrosine phosphorylation and increased its autophosphorylation activity. Experiments with altered erythropoietin receptors connected these changes with the ability to stimulate cell multiplication. This supplied a concrete mechanism for signal transduction: a receptor without an intrinsic kinase protein domain can recruit a separate protein kinase. The combination of physical association, regulated activity and altered-receptor tests is more informative than any one measurement alone.[ref]
JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin by B. A. Witthuhn and others. Abstract: receptor mutants, JAK2 association and activation correlated with mitogenesis
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