A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes.
A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes.
复制标题
人类集落刺激因子 1 受体中酪氨酸 809 处的点突变会损害有丝分裂，但不会消除酪氨酸激酶活性、与磷脂酰肌醇 3-激酶的关联或 c-fos 和 junB 基因的诱导。
DOI：
10.1073/pnas.87.17.6738
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Sherr,CJ
中科院分区：
文献类型：
--
作者：
Roussel,MF;Shurtleff,SA;Downing,JR;Sherr,CJ
人集落刺激因子1受体(CSF-1R)中苯丙氨酸取代酪氨酸-809抑制了其在小鼠NIH3T3细胞中转导配体依赖的有丝分裂信号的能力。当结合301密码子的“激活”突变，诱导结构性的CSF-1R酪氨酸激酶活性时，密码子809突变抑制了非配体依赖的细胞转化。对突变型和野生型CSF-1R的胰酶磷酸肽的比较定位表明，酪氨酸-809是体内配体依赖的受体磷酸化的位点。突变的受体在体外和体内都是作为酪氨酸激酶活跃的，经历了依赖于CSF-1与磷脂酰肌醇3-激酶的结合，并诱导了原癌基因c-fos和JunB的表达，突显了它触发一些已知的细胞对CSF-1的反应的能力。突变的受体很可能在与关键的细胞效应器相互作用的能力方面受到损害，这些效应器的活性是有丝分裂发生所必需的。
Substitution of phenylalanine for tyrosine-809 in the human colony-stimulating factor 1 receptor (CSF-1R) inhibited its ability to transduce ligand-dependent mitogenic signals in mouse NIH 3T3 cells. When combined with an "activating" mutation at codon 301 that induces constitutive CSF-1R tyrosine kinase activity, the codon 809 mutation suppressed ligand-independent cell transformation. Comparative mapping of tryptic phosphopeptides from mutant and wild-type CSF-1R indicated that tyrosine-809 is a site of ligand-dependent receptor phosphorylation in vivo. The mutant receptor was active as a tyrosine kinase in vitro and in vivo, underwent CSF-1-dependent association with a phosphatidylinositol 3-kinase, and induced expression of the protooncogenes c-fos and junB, underscoring its ability to trigger some of the known cellular responses to CSF-1. The mutant receptor is likely to be impaired in its ability to interact with critical cellular effectors whose activity is required for mitogenesis.