Dominant negative effects of a carboxy-truncated Jak2 mutant on Epo-induced proliferation and Jak2 activation.
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.
Zhuang
H
H
Department of Biochemistry & Molecular Biology and Veterinary Science, Pennsylvania State University, University Park 16802.
Patel
S V
SV
He
T C
TC
Niu
Z
Z
Wojchowski
D M
DM
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D053614:Janus Kinase 2; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016364:Reading Frames; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D017384:Sequence Deletion; D013728:Terminator Regions, Genetic; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2