Members of the Janus family of protein tyrosine kinases are emerging as primary, receptor-associated transducing factors among numerous cytokine systems. However, little is understood regarding mechanisms of recruitment of these kinases to receptor complexes and their ligand-dependent activation. To initially address these questions, we have assessed effects of ectopically expressing a carboxy-truncated form of Jak2 (Jak2-829) in Epo-responsive DAER cells. Expression of this truncation mutant at low levels efficiently inhibited both Epo-dependent activation of endogenous Jak2 and Epo-induced mitogenesis (10% to 39% of parental DAER cells). These results suggest that amino-terminal domains of Jak2 may mediate the assembly of Jak2/Epo receptor complexes and that integration of Jak2-829 into receptor complexes may effectively inhibit the activity of oligomeric Jak2/receptor assemblages.
