RECOVERY OF MITOGENIC ACTIVITY OF A GROWTH-FACTOR MUTANT WITH A NUCLEAR TRANSLOCATION SEQUENCE
RECOVERY OF MITOGENIC ACTIVITY OF A GROWTH-FACTOR MUTANT WITH A NUCLEAR TRANSLOCATION SEQUENCE
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DOI：
10.1126/science.1699274
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发表时间：
1990-09-28
期刊：
影响因子：
56.9
通讯作者：
MACIAG, T
中科院分区：
文献类型：
--
作者：
IMAMURA, T;ENGLEKA, K;MACIAG, T
肝素结合生长因子-1（HBGF-1）是用于体外中胚层和神经外胚层衍生的细胞的血管生成多肽促分裂原，并且在氨基末端结构域（HBGF-1 α）截短后保持生物活性。的HBGF-1 β。先驱使用聚合酶链反应诱变和原核表达系统制备HBGF-1 α的突变体。缺乏推定的核易位序列（氨基酸残基21至27; HBGF-1U）。尽管HBGF-1U保留了与肝素结合的能力，但在足以诱导细胞内受体介导的酪氨酸磷酸化和c-fos表达的浓度下，HBGF-1U无法诱导DNA合成和细胞增殖。将来自酵母组蛋白2B的核转位序列连接在HBGF-1U的氨基末端产生具有体外促有丝分裂活性的嵌合多肽（HBGF-1U 2），并表明核转位对于这种生物学反应是重要的。
Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1.alpha.) of the HBGF-1.beta. precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1.alpha. lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.