INTERLEUKIN-3 SIGNALS THROUGH MULTIPLE ISOFORMS OF STAT5
INTERLEUKIN-3 SIGNALS THROUGH MULTIPLE ISOFORMS OF STAT5
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DOI：
10.1002/j.1460-2075.1995.tb07126.x
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发表时间：
1995-04-03
期刊：
影响因子：
11.4
通讯作者：
SCHINDLER, C
中科院分区：
文献类型：
--
作者：
AZAM, M;ERDJUMENTBROMAGE, H;SCHINDLER, C
白细胞介素（IL）-3家族的细胞因子介导其对骨髓生长和成熟的许多影响，通过结合一个家庭的相关受体。最近已经表明，IL-3诱导两种不同的细胞质信号转导因子（STFs）的活化，所述细胞质信号转导因子可能介导立即早期基因的诱导。在未成熟的骨髓细胞中，IL-3激活STF-IL-3a，其包含77和80 kDa的两种酪氨酸磷酸化DNA结合蛋白。在成熟的骨髓细胞中，IL-3和粒细胞-巨噬细胞集落刺激因子激活STF-IL-3b，其由94和96 kDa酪氨酸磷酸化DNA结合蛋白组成。从纯化的77和80 kDa蛋白质（p77和p80）获得的肽序列数据表明它们密切相关，但由不同的基因编码。肽和核苷酸序列数据表明，这两种蛋白质是绵羊乳腺因子（MGF）/Stat 5的鼠同源物。肽数据还表明p77和p80在酪氨酸699上磷酸化，该位置类似于响应干扰素而在Stat 1和Stat 2中磷酸化的酪氨酸。此外，针对细菌表达的p77/p80产生的抗血清识别STF-IL-3b的94和96 kDa蛋白组分，表明这些可能是Stat 5的其他同种型。这些研究表明IL-3配体家族能够激活信号转导蛋白Stat 5的多种同种型。
The interleukin (IL)-3 family of cytokines mediates its numerous effects on myeloid growth and maturation by binding a family of related receptors. It has been shown recently that IL-3 induces the activation of two distinct cytoplasmic signal transducing factors (STFs) that are likely to mediate the induction of immediate early genes. In immature myeloid cells, IL-3 activates STF-IL-3a, which comprises two tyrosine-phosphorylated DNA binding proteins of 77 and 80 kDa. In mature myeloid cells, IL-3 and granulocyte-macrophage colony-stimulating factor activate STF-IL-3b, which consists of a 94 and 96 kDa tyrosine-phosphorylated DNA binding protein. Peptide sequence data obtained from the purified 77 and 80 kDa proteins (p77 and p80) indicate that they are closely related but are encoded by distinct genes. Both peptide and nucleotide sequence data demonstrate that these two proteins are the murine homologs of ovine mammary gland factor (MGF)/Stat5. The peptide data also indicate that p77 and p80 are phosphorylated on tyrosine 699, a position analogous to the tyrosine that is phosphorylated in Stat1 and Stat2 in response to interferon. Additionally, antiserum raised against bacterially expressed p77/p80 recognizes the 94 and 96 kDa protein components of STF-IL-3b, suggesting that these may be additional isoforms of Stat5. These studies indicate that the IL-3 family of ligands is able to activate multiple isoforms of the signal transducing protein Stat5.