Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain.
Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain.
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FMA3 鼠肥大细胞瘤细胞中 c-kit 的组成型激活是由近膜结构域的 7 个氨基酸缺失引起的。
DOI：
10.1182/blood.v87.1.273.273
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发表时间：
1996
期刊：
影响因子：
20.3
通讯作者：
Y. Kanakura
中科院分区：
文献类型：
--
作者：
T. Tsujimura;M. Morimoto;K. Hashimoto;Y. Moriyama;H. Kitayama;Y. Matsuzawa;Y. Kitamura;Y. Kanakura
一种特殊的点突变导致三种不同肿瘤肥大细胞系（即HMC-1、P-815和RBL-2 H3）中c-kit受体酪氨酸激酶（KIT）的组成性激活。由于在FMA 3小鼠肥大细胞瘤细胞系中也观察到KIT的组成性激活，因此我们研究了其分子机制。对c-kit的整个编码区的测序表明，在HMC-1、P-815和RBL-2 H3细胞中发现的点突变在FMA 3细胞中不存在，并且FMA 3细胞的c-kit cDNA在胞膜结构域的密码子573至579处携带编码Thr-Gln-Leu-Pro-Tyr-Asp-His的21个碱基对（bp）的框内缺失。将具有21 bp缺失的FMA 3型c-kit cDNA导入IC-2细胞系中，该细胞系来源于小鼠培养的肥大细胞。IC-2细胞依赖于白细胞介素（IL）-3，表面不表达KIT。在引入FMA 3型c-kit cDNA的IC-2细胞中，KIT在酪氨酸上组成性磷酸化并被激活。此外，FMA 3型KIT在没有干细胞因子（SCF）（KIT的配体）刺激的情况下二聚化。没有SCF结合的自发二聚化的FMA 3型KIT即使在活化后也没有内化。表达FMA 3型KIT的IC-2细胞在无IL-3和SCF的悬浮培养中生长，并在裸鼠中变成白血病。在肥大细胞的细胞膜结构域的7个氨基酸的缺失似乎是一个新的激活突变的KIT，可能参与肥大细胞的肿瘤生长。
A peculiar point mutation results in constitutive activation of c-kit receptor tyrosine kinase (KIT) in three different tumor mast cell lines; ie, the HMC-1, P-815, and RBL-2H3. Because constitutive activation of KIT was also observed in the FMA3 mouse mastocytoma cell line, we investigated the molecular mechanism. Sequencing of the whole coding region of the c-kit showed that the point mutation found in HMC-1, P-815, and RBL-2H3 cells was absent in FMA3 cells and that the c-kit cDNA of FMA3 cells carried an in-frame deletion of 21 base pairs (bp) encoding Thr-Gln-Leu-Pro-Tyr-Asp-His at codons 573 to 579 at the juxtamembrane domain. The FMA3-type c-kit cDNA with 21 bp deletion was introduced into the IC-2 cell line, which was derived from murine cultured mast cells. IC-2 cells were dependent on interleukin (IL)-3 and did not express KIT on the surface. In IC-2 cells introduced with the FMA3-type c-kit cDNA, KIT was constitutively phosphorylated on tyrosines and activated. Moreover, the FMA3-type KIT was dimerized without the stimulation by stem cell factor (SCF), a ligand for KIT. The spontaneously dimerized FMA3-type KIT without SCF binding was not internalized even after the activation. IC-2 cells expressing the FMA3-type KIT grew in suspension culture without IL-3 and SCF and became leukemic in nude athymic mice. The deletion of seven amino acids at the juxtamembrane domain appeared to be a new activating mutation of KIT that might be involved in neoplastic growth of mast cells.
小鼠 B 淋巴细胞上含有多个 B29 复合物。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ishihara,K;WoodJr,WJ;Wall,R;Sakaguchi,N;Michnoff,C;Tucker,PW;Kincade,PW
通讯作者：
Kincade,PW
小鼠血小板衍生生长因子α受体：序列、组织特异性表达及其与转移表型的相关性。
影响因子：
8
作者：
Do,MS;Fitzer-Attas,C;Gubbay,J;Greenfeld,L;Feldman,M;Eisenbach,L
通讯作者：
Eisenbach,L
人粒细胞-巨噬细胞集落刺激因子和白细胞介素 3 受体的信号转导涉及一组常见细胞质蛋白的酪氨酸磷酸化。
影响因子：
20.3
作者：
Kanakura,Y;Druker,B;Cannistra,SA;Furukawa,Y;Torimoto,Y;Griffin,JD
通讯作者：
Griffin,JD