Differential regulation of the alpha 2 beta 1 and alpha IIb beta 3 integrin genes during megakaryocytic differentiation of pluripotential K562 cells.
Expression of the alpha 2 beta 1 and alpha IIb beta 3 integrin genes is differentially regulated during megakaryocytic differentiation of pluripotent K562 cells induced with phorbol 12,13-dibutyrate. Upon megakaryocytic differentiation, steady-state alpha 2 mRNA increased markedly from the undetectable level present in the uninduced cells. The level of beta 1 mRNA did not change. Expression of alpha IIb beta 3 is regulated differently. beta 3 mRNA was undetectable in uninduced cells but increased significantly following induction. alpha 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 alpha 2 gene transcription upon megakaryocytic differentiation, but no change in transcription of the beta 1 gene. Transcription of both the alpha IIb and beta 3 genes increased 10- and 5-fold, respectively. Thus, the increase in alpha 2 beta 1 protein which accompanies the megakaryocytic differentiation of K562 cells is a consequence of the increased steady-state level of alpha 2 mRNA due to transcriptional activation of the alpha 2 gene. The long-lived beta 1 mRNA is not altered during differentiation. In contrast, increased alpha IIb beta 3 protein appears due to increased steady-state levels of both alpha IIb and beta 3 mRNAs that result from transcriptional activation of both integrin genes.
Zutter
M M
MM
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Fong
A M
AM
Krigman
H R
HR
Santoro
S A
SA
D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D016023:Integrins / Q000235:genetics*; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D016023:Integrins; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D003094:Collagen