1. Assembly and Activation of an Erythropoietin Receptor (EpoR) Signaling Complex HARVEY F. LODISH, Professor of Biology and Professor of Biological Engineering, M.I.T. Member, Whitehead Institute for Biomedical Research, Cambridge, MA
Erythropoietin (Epo) is the principal hormone regulating production of red blood cells. Epo production by the kidney is enhanced by anoxia, and it functions by inhibiting apoptosis of a class of committed erythroid progenitors. The erythropoietin receptor, like all cytokine receptors, requires a JAK tyrosine kinase protein for signal transduction. In the resting state cell surface EpoR is a dimer and Epo binding alters the conformations of the two receptor extracellular domains.
We showed that JAK2, more specifically just its NH2-terminal “FERM” domain, binds in the endoplasmic reticulum to the membrane-proximal cytosolic domain of newly made EpoR to promote receptor folding and cell surface expression. The amount of JAK2 is thus one of the factors that...
