Co-ordinate expression of activin A and its type I receptor mRNAs during phorbol ester-induced differentiation of human K562 erythroleukemia cells.
Activins were originally isolated based on their ability to stimulate follicle-stimulating hormone secretion but later they have been shown to regulate a number of different cellular functions such as nerve cell survival, mesoderm induction during early embryogenesis as well as hematopoiesis. We studied the regulation of activin A, a homodimer of betaA-subunits, mRNA and protein in K562 erythroleukemia cells, which are known to be induced toward the erythroid lineage in response to activin or TGF-beta or toward the megakaryocytic lineage by the phorbol ester protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). Here we show by Northern blot analysis as well as by Western and ligand blotting that TPA strongly promotes activin betaA-subunit mRNA and activin A protein expression in K562 cells in time- and concentration dependent manner. In contrast, neither activin A nor TGF-beta induced betaA-subunit mRNA expression during erythroid differentiation in K562 cells. Interestingly, whereas activin type II receptors are not regulated during K562 cell differentiation (Hilden et al. (1994) Blood 83, 2163-2170), we now show that the activin type I and IB receptor mRNAs are clearly induced by TPA but not by activin or TGF-beta. We also show that the inducing effect of TPA on expression of activin betaA-subunit mRNA is potentiated by the protein kinase A activator 8-bromo-cAMP. We conclude that activin A and its type I receptors appear to be co-ordinately up-regulated during megakaryocytic differentiation of K562 cells.
Hildén
K
K
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland.
Tuuri
T
T
Erämaa
M
M
Ritvos
O
O
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D029404:Activin Receptors; D028341:Activins; D015139:Blotting, Southern; D002454:Cell Differentiation; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019281:Dimerization; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007265:Inhibins / Q000235:genetics*; D020014:K562 Cells / Q000166:cytology / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D028341:Activins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007265:Inhibins; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D029404:Activin Receptors; D013755:Tetradecanoylphorbol Acetate