PLCbeta1a and PLCbeta1b selective regulation and cyclin D3 modulation reduced by Kinamycin F during K562 cell differentiation.

Here we report that both PLCbeta1a and PLCbeta1b are relevant regulators of erythropoiesis in that kinamycin F, a potent inducer of gamma-globin production in K562 cells, caused a selectively reduction of both PLCbeta1 isozymes even though the results point out that the effect of the drug is mainly directed toward the expression of the PLCbeta1a isoform. We have identified a different role for the two isozymes as regulators of K562 differentiation process induced by kinamycin F. The overexpression of PLCbeta1b induced an increase in gamma-globin expression even in the absence of kinamycin F. Moreover during K562differentiation, cyclin D3 level is regulated by PLCbeta1 signaling pathway. Namely the amplification of the expression of the PLCbeta1a, but not of PLCbeta1b, is able to maintain high levels of expression of cyclin D3 even after treatment with kinamycin F. This could be due to their different distribution in the cell compartments since the amount of PLCbeta1b is mainly present in the nucleus in respect to PLCbeta1a. Our data indicate that the amplification of PLCbeta1a expression, following treatment withkinamycin F, confers a real advantage to K562 cells viability and protects cells themselves from apoptosis. 2014 Wiley Periodicals, Inc., A Wiley Company