TRANSFORMATION OF ERYTHROID PROGENITORS BY VIRAL AND CELLULAR TYROSINE KINASES

Recently, two different normal avian erythroid progenitors were descri bed. They differ in the receptor tyrosine kinases they express and in their ability to undergo self-renewal in culture. A common progenitor, termed stem cell factor (SCF) progenitor, expresses the receptor for avian SCF c-Kit, and undergoes short-term self-renewal when grown in t he presence of avian SCF. A second progenitor, referred to as SCF/tran sforming growth factor-alpha progenitor, coexpresses c-Kit and the avi an epidermal growth factor receptor homologue c-ErbB. These progenitor s undergo sustained self-renewal when grown in the presence of transfo rming growth factor-alpha plus estradiol. The phenotype of the normal SCF/transforming growth factor-alpha progenitors closely corresponded to that of erythroid cells transformed by the tyrosine kinase oncogene s v-erbs or v-sea. This suggested that these cells, but not the SCF pr ogenitors, would be the target cells for erythroblast transformation b y these oncogenes. However, we demonstrate that both progenitor cells can be transformed by the v-erbB and v-sea oncogenes and also by the l igand-activated protooncogene product c-ErbB. We conclude that the tar get cell specificity of certain tyrosine kinase oncoproteins for eryth roid cells is a reflection of their ability to provide signals for sel f-renewal that normally emaciate from the endogenous c-ErbB protein.