THE BETA-PDGF RECEPTOR INDUCES NEURONAL DIFFERENTIATION OF PC12 CELLS
THE BETA-PDGF RECEPTOR INDUCES NEURONAL DIFFERENTIATION OF PC12 CELLS
复制标题
DOI：
10.1091/mbc.3.5.545
复制
发表时间：
1992-05-01
影响因子：
3.3
通讯作者：
JOHNSON, GL
中科院分区：
文献类型：
--
作者：
HEASLEY, LE;JOHNSON, GL
通过基因转移表达小鼠 β-PDGF 受体可赋予 PC12 嗜铬细胞瘤细胞 PDGF 依赖性和可逆性神经元分化，类似于对 NGF 和碱性 FGF 的反应中观察到的情况。 PDGF、NGF 和基本 FGF 诱导的分化反应的一个共同特性是需要细胞持续暴露于生长因子。为了检验维持神经元表型需要持续水平的生长因子受体信号传导的假设，我们检查了生长因子短期（10 分钟）或长期（24 小时）刺激后丝氨酸/苏氨酸特异性 MAP 激酶的调节。 Mono Q FPLC 解析了生长因子刺激的 MAP 激酶活性的两个峰，该活性与酪氨酸磷酸化的 41-和 43-kDa 多肽共洗脱。 MAP 激酶活性在暴露于多种生长因子（PDGF、NGF、碱性 FGF、EGF 和 IGF-I）后 5 分钟内显着刺激（约 30 倍），但在 24 小时后仅通过也诱导 PC12 细胞分化的生长因子（PDGF、NGF 和碱性 FGF）持续维持在基础活性的 10 倍以上。因此，β-PDGF 受体属于酪氨酸激酶编码的生长因子受体的一个子集，能够维持 PC12 细胞分化所需的连续信号。这些信号包括细胞质丝氨酸/苏氨酸蛋白激酶的组成型激活。
Expression of the mouse beta-PDGF receptor by gene transfer confers PDGF-dependent and reversible neuronal differentiation of PC12 pheochromocytoma cells similar to that observed in response to NGF and basic FGF. A common property of the PDGF, NGF, and basic FGF-induced differentiation response is the requirement for constant exposure of cells to the growth factor. To test the hypothesis that a persistent level of growth factor receptor signaling is required for the maintenance of the neuronal phenotype, we examined the regulation of the serine/threonine-specific MAP kinases after either short- (10 min) or long-term (24 h) stimulation with growth factors. Mono Q FPLC resolved two peaks of growth factor-stimulated MAP kinase activity that coeluted with tyrosine phosphorylated 41- and 43-kDa polypeptides. MAP kinase activity was markedly stimulated (approximately 30-fold) within 5 min of exposure to several growth factors (PDGF, NGF, basic FGF, EGF, and IGF-I), but was persistently maintained at 10-fold above basal activity after 24 h only by the growth factors that also induce PC12 cell differentiation (PDGF, NGF, and basic FGF). Thus the beta-PDGF receptor is in a subset of tyrosine kinase-encoded growth factor receptors that are capable of maintaining continuous signals required for differentiation of PC12 cells. These signals include the constitutive activation of cytoplasmic serine/threonine protein kinases.