PLCβ1a and PLCβ1b Selective Regulation and Cyclin D3 Modulation Reduced by Kinamycin F During K562 Cell Differentiation

Abstract

Here we report that both PLCβ1a and PLCβ1b are relevant regulators of erythropoiesis in that kinamycin F, a potent inducer of γ-globin production in K562 cells, caused a selectively reduction of both PLCβ1 isozymes even though the results point out that the effect of the drug is mainly directed toward the expression of the PLCβ1a isoform. We have identified a different role for the two isozymes as regulators of K562 differentiation process induced by kinamycin F. The overexpression of PLCβ1b induced an increase in γ-globin expression even in the absence of kinamycin F. Moreover during K562 differentiation, cyclin D3 level is regulated by PLCβ1 signaling pathway. Namely the amplification of the expression of the PLCβ1a, but not of PLCβ1b, 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 PLCβ1b is mainly present in the nucleus in respect to PLCβ1a. Our data indicate that the amplification of PLCβ1a expression, following treatment with kinamycin F, confers a real advantage to K562 cells viability and protects cells themselves from apoptosis.

The atypical ‘b’ splice variant of phospholipase Cβ1 promotes cardiac contractile dysfunction

“…Our studies have demonstrated this to be the case in cardiomyocytes (Fig. 1E) [20], and others have reported different localizations in a cultured lymphoma cell line [35]. In contrast, in CHO cells and PC12 cells, PLCβ1a and PLCβ1b are both localized at the plasma membrane [36].…”

BMP‐2 Induced Expression of PLCβ1 That is a Positive Regulator of Osteoblast Differentiation

“…PLCβ1 gene is expressed as alternatively spliced variants β1a and β1b, which are dissimilar in their C‐terminal residues. PLCβ1a is concentrated preferentially in the cytosol, while PLCβ1b is localized mainly in the nucleus (Faenza et al, ; Bavelloni et al, ). Recently, the nuclear protein interaction network of PLCβ1b was analyzed, evidencing the presence of multiprotein complexes in which PLCβ1b was connected with proteins required for cellular metabolic processes (e.g., response to oxidative stress), nuclear transport, and regulation of apoptosis (Piazzi et al, ).…”

Nuclear Phosphatidylinositol Signaling: Focus on Phosphatidylinositol Phosphate Kinases and Phospholipases C

“…Erythroid differentiation of K562 cells was characterized by an important decrease of PLCβ1 levels followed by the increase in mir‐210 and γ‐globin levels, two important markers of K562 erythroid differentiation (Cioe et al, ; Bianchi et al, ; Bavelloni et al, ). Modulation of nuclear PLCβ1 led to direct regulation of the expression of these two molecules, and, in turn, of erythroid differentiation (Bavelloni et al, ). Furthermore, recent findings showed that erythroid differentiation of CD34 cells following erythropoietin (EPO) treatment was noticeably inhibited by PLCβ1 overexpression (Follo et al, , ).…”