Schubart U K, Xu J, Fan W, Cheng G, Goldstein H, Alpini G, Shafritz D A, Amat J A, Farooq M, Norton W T
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Differentiation. 1992 Sep;51(1):21-32. doi: 10.1111/j.1432-0436.1992.tb00676.x.
p19 is a highly conserved 19 kD cytosolic protein that undergoes phosphorylation in response to diverse extracellular factors in mammalian cells. Its expression is abundant in brain and testis and is developmentally regulated. To gain insights regarding its function, we analyzed the expression of p19 mRNA in a variety of cell types during induction of differentiation. Murine erythroleukemia cells showed a moderate increase followed by a marked decrease in the abundance of p19 mRNA during induction of differentiation. In murine C2 myoblasts and primary fetal rat osteoblasts, p19 mRNA was abundant in replicating cells and decreased to undetectable levels during differentiation. In resting human peripheral blood lymphocytes, p19 mRNA was virtually undetectable but was strongly induced during blast transformation of both B and T cells. In rat liver, p19 mRNA was abundant on embryonic day 17 and decreased during early postnatal development. Upon fractionation of adult rat liver cells by centrifugal elutriation, p19 mRNA was not detected in hepatocytes while a low level was observed in a fraction enriched in non-parenchymal epithelial cells. CCl4-induced liver regeneration resulted in induction of p19 mRNA in hepatocytes. Primary cultures of embryonic and neonatal rat brain were analyzed by indirect immunofluorescence using co-staining with stage-specific markers. p19 expression was restricted to immature neurons and oligodendrocyte precursors. In contrast to the other cell types examined, the neuronal and glial precursors that express p19 were shown, using BrdU labeling, to be postmitotic both in primary culture and in vivo. The data demonstrate widespread, stage-specific expression of p19 and suggest that the protein exerts a general, lineage-independent function during induction of differentiation of mammalian cells. In view of the available evidence on the stimulation of serine phosphorylation of p19 by several growth factors, our working hypothesis is that phosphorylation of p19 may be involved in the mechanism by which growth factors control cell differentiation.
p19是一种高度保守的19 kD胞质蛋白，在哺乳动物细胞中，它会响应多种细胞外因子而发生磷酸化。其在脑和睾丸中表达丰富，并受发育调控。为深入了解其功能，我们分析了分化诱导过程中多种细胞类型中p19 mRNA的表达情况。在分化诱导过程中，小鼠红白血病细胞中p19 mRNA的丰度先适度增加，随后显著下降。在小鼠C2成肌细胞和原代胎鼠成骨细胞中，p19 mRNA在增殖细胞中丰富，在分化过程中降至不可检测水平。在静息的人外周血淋巴细胞中，p19 mRNA几乎不可检测，但在B细胞和T细胞的母细胞转化过程中被强烈诱导。在大鼠肝脏中，p19 mRNA在胚胎第17天丰富，在出生后早期发育过程中下降。通过离心淘洗对成年大鼠肝细胞进行分级分离后，在肝细胞中未检测到p19 mRNA，而在富含非实质上皮细胞的部分中观察到低水平表达。四氯化碳诱导的肝脏再生导致肝细胞中p19 mRNA的诱导表达。使用阶段特异性标记物共染色，通过间接免疫荧光分析胚胎和新生大鼠脑的原代培养物。p19表达仅限于未成熟神经元和少突胶质细胞前体。与其他检查的细胞类型不同，使用BrdU标记显示，在原代培养和体内表达p19的神经元和神经胶质前体均为有丝分裂后细胞。数据表明p19存在广泛的、阶段特异性表达，并表明该蛋白在哺乳动物细胞分化诱导过程中发挥一般的、不依赖谱系的功能。鉴于现有证据表明几种生长因子可刺激p19的丝氨酸磷酸化，我们的工作假设是p19的磷酸化可能参与生长因子控制细胞分化的机制。
