Activation of phosphatidylinositol 3-kinase is necessary for differentiation of FDC-P1 cells following stimulation of type III receptor tyrosine kinases.
Activation of phosphatidylinositol 3-kinase is necessary for differentiation of FDC-P1 cells following stimulation of type III receptor tyrosine kinases.
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在刺激 III 型受体酪氨酸激酶后，磷脂酰肌醇 3-激酶的激活对于 FDC-P1 细胞的分化是必需的。
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
A. Ullrich
中科院分区：
文献类型：
--
作者：
Y. Kubota;Timothy Angelotti;G. Niederfellner;R. Herbst;A. Ullrich
在白细胞介素3 （IL-3）依赖的造血细胞系FDC-P1中，研究了受体酪氨酸激酶（RTKs）异位表达后造血细胞增殖和分化的信号分子。细胞转染了人血小板衍生生长因子受体（PDGF-R）、巨噬细胞集落刺激因子-1受体（CSF-1R）、表皮生长因子受体（EGF-R），以及由EGF-R的细胞外结构域和HER2 （HER1-2）或c-kit （EK-R）的跨膜和胞质结构域组成的嵌合体。在没有IL-3的情况下，所有FDC-P1转染物都对相应的生长因子有增殖反应。然而，只有表达PDGF-R、CSF-1R和EK-R的细胞（III型rtk）在其激活配体处理后沿单核-巨噬细胞谱系分化。对这些rtk表达细胞的蛋白进行分析，发现Mr为85000的蛋白在体外被磷酸化，V8蛋白酶肽图谱显示该蛋白是磷脂酰肌醇3-激酶（pi3 -激酶）的调控亚基p85。因此，PDGF-R-、CSF-1R-和ek - r表达细胞的激活导致pi3激酶活性增加。缺乏已知p85结合位点的EK-R突变体Y721F的表达阻断了pi3激酶的分化和激活，但不影响增殖。最后，将wortmannin添加到表达PDGF-R、CSF-1R和ekr的细胞中，以浓度依赖的方式阻断配体诱导的分化，这种作用与wortmannin抑制pi3激酶的能力相关。因此，在缺乏IL-3的情况下，I型和III型rtk的异位表达都可以刺激FDC-P1的增殖；然而，只有III型rtk的激活通过选择性偶联p85和pi3激酶激活导致分化。
Signaling molecules that are responsible for proliferation and differentiation of hematopoietic cells following ectopic expression of receptor tyrosine kinases (RTKs) were investigated in the interleukin 3 (IL-3)-dependent hematopoietic cell line, FDC-P1. Cells were transfected with human platelet-derived growth factor receptor (PDGF-R), macrophage colony stimulating factor-1 receptor (CSF-1R), epidermal growth factor receptor (EGF-R), and chimeras consisting of the extracellular domain of EGF-R and the transmembrane and cytoplasmic domains of either HER2 (HER1-2) or c-kit (EK-R). All FDC-P1 transfectants proliferated in response to the corresponding growth factor in the absence of IL-3. However, only cells expressing PDGF-R, CSF-1R, and EK-R (type III RTKs) differentiated along the monocyte-macrophage lineage after treatment with their activating ligands. Analysis of proteins from these RTK-expressing cells revealed that a Mr 85,000 protein showed in vitro phosphorylation, and V8 protease peptide mapping showed that this protein was p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase). Accordingly, activation of PDGF-R-, CSF-1R-, and EK-R-expressing cells led to an increase in PI3-kinase activity. Expression of EK-R mutant Y721F, which lacked the known p85 binding site, blocked differentiation and activation of PI3-kinase, without affecting proliferation. Last, addition of wortmannin to cells expressing PDGF-R, CSF-1R, and EK-R blocked ligand-induced differentiation in a concentration-dependent manner, and this effect correlated with wortmannin's ability to inhibit PI3-kinase. Thus, ectopic expression of both type I and III RTKs could stimulate FDC-P1 proliferation in the absence of IL-3; however, only activation of type III RTKs led to differentiation via selective coupling to p85 and PI3-kinase activation.
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trk 癌基因消除生长因子需求并转化造血细胞。
影响因子：
8
作者：
Katzav,S;Martin-Zanca,D;Barbacid,M;Hedge,AM;Isfort,R;Ihle,JN
通讯作者：
Ihle,JN
v-fms 癌基因诱导白细胞介素 3 依赖性骨髓细胞系 FDC-P1 的不依赖于因子的生长和转化。
影响因子：
5.3
作者：
Wheeler,EF;Askew,D;May,S;Ihle,JN;Sherr,CJ
通讯作者：
Sherr,CJ
骨髓 FDC-P1 细胞中表达的鼠巨噬细胞集落刺激因子受体介导的增殖和分化信号的解偶联。
DOI：
--
发表时间：
1995
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.
影响因子：
--
作者：
Bourette,RP;Myles,GM;Carlberg,K;Chen,AR;Rohrschneider,LR
通讯作者：
Rohrschneider,LR
集落刺激因子 (CSF-1) 的纯化、测定、表征和靶细胞结合的方法。
影响因子：
2.2
作者：
Stanley,ER;Guilbert,LJ
通讯作者：
Guilbert,LJ