ERYTHROPOIETIN ACTIVATION OF AP1 (FOS JUN)

Erythropoietin (Epo) is the principal natural inducer of erythroid dif ferentiation. The mechanisms by which signals generated at the Epo rec eptor (Epo-R) are transmitted to the nucleus are being explored. We no w report that Epo strongly increases the activity of the transcription factor AP1 in both transformed and normal erythroid cells. Using anti bodies to Fos and Jun, we have found that the Epo-induced AP1 heterodi mer is composed primarily of authentic Fos and Jun proteins. Blocking protein kinase C (PKC) activity with H7 completely prevented the incre ase in AP1 activity in response to Epo. Importantly, the increase in A P1 activity was not due to increased expression of either c-fos or c-j un, as evidenced by the steady-state mRNA levels of both genes. Our re sults suggest that Epo may induce AP1 activity via a co- or post-trans lational mechanism, presumably through modification of the Fos and/or Jun proteins.