Differential regulation of the α₂β₁ and α_IIbβ₃ integrin genes during megakaryocytic differentiation of pluripotential K562 cells

Expression of the α₂β₁ and α_IIbβ₃ integrin genes is differentially regulated during megakaryocytic differentiation of pluripotent K562 cells induced with phorbol 12,13-dibutyrate. Upon megakaryocytic differentiation, steady-state α₂ mRNA increased markedly from the undetectable level present in the uninduced cells. The level of β₁ mRNA did not change. Expression of α_IIbβ₃ is regulated differently. β₃ mRNA was undetectable in uninduced cells but increased significantly following induction. α_IIb mRNA was detectable at a low level prior to induction, but at an increased level following differentiation. Altered mRNA stability did not contribute to changes in mRNA levels. Nuclear run-off experiments revealed a 20-fold increase in α₂ gene transcription upon megakaryocytic differentiation, but no change in transcription of the β₁ gene. Transcription of both the α_IIb and β₃ genes increased 10- and 5-fold, respectively. Thus, the increase in α₂β₁ protein which accompanies the megakaryocytic differentiation of K562 cells is a consequence of the increased steady-state level of α₂ mRNA due to transcriptional activation of the α₂ gene. The long-lived β₁ mRNA is not altered during differentiation. In contrast, increased α_IIbβ₃ protein appears due to increased steady-state levels of both α_IIb and β₃ mRNAs that result from transcriptional activation of both integrin genes.