Activation of renal erythropoietic factor by phosphorylation.

Renal erythropoietic factor (REF) serves as a substrate for a cyclic nucleotide-dependent protein kinase. The phosphorylation of REF is associated with increased erythropoietic activity. Conversely, REF isolated from hypoxic rats is a poor phosphate acceptor. These findings and the presence of a positive correlation between erythropoietin levels and urinary excretion of adenosine 3',5' monophosphate (cyclic-AMP) in anemic individuals suggest that the cyclic-AMP-protein kinase system plays an important role in the activation of REF.