TAB1β (transforming growth Factor-β-activated protein kinase 1-binding protein 1β), a novel splicing variant of TAB1 that interacts with p38α but not TAK1
TAB1β (transforming growth Factor-β-activated protein kinase 1-binding protein 1β), a novel splicing variant of TAB1 that interacts with p38α but not TAK1
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DOI：
10.1074/jbc.m210918200
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发表时间：
2003-01-24
影响因子：
4.8
通讯作者：
Han, JH
中科院分区：
文献类型：
--
作者：
Ge, BX;Xiong, XS;Han, JH
丝裂原激活蛋白激酶（MAPK）在多种生物过程中发挥着重要作用。 MAPK 的激活是通过特定酪氨酸和苏氨酸位点的磷酸化介导的。我们最近发现p38α MAPK的激活不仅可以通过其上游MAPK激酶（MKK）来进行，还可以通过p38α自身磷酸化来进行。 p38α 自动激活需要 p38α 与 TAB1（转化生长因子-β 激活蛋白激酶 1 结合蛋白 1）相互作用。已发现 p38α 的自动激活机制在细胞对许多生理相关刺激的反应中非常重要。在这里，我们报告了 TAB1 剪接变体 TAB1beta 的表征。 TAB1 和 TAB1beta 共享前 10 个外显子。 TAB1β中TAB1的第11和第12外显子被剪接掉，基因组中第11和12号外显子下游的一个额外的外显子，称为外显子β，被用作TAB1β的最后一个外显子。 TAB1beta 的 mRNA 在所有检查的细胞系中都有表达。 TAB1beta mRNA 编码的蛋白质与 TAB1 具有相同的序列，只是 C 端 69 个氨基酸被替换为不相关的 27 个氨基酸序列。与 TAB1 类似，TAB1beta 与 p38alpha 相互作用，但不与其他 MAPK 相互作用，并刺激 p38alpha 自动激活。与 TAB1 不同，TAB1beta 不结合或激活 TAK1。在MDA231乳腺癌细胞中通过RNA干扰抑制TAB1β表达导致p38α基础活性降低和MDA231细胞侵袭性降低，表明TAB1β参与生理条件下p38α活性的调节。
The mitogen-activated protein kinases (MAPKs) play an important role in a variety of biological processes. Activation of MAPKs is mediated by phosphorylation on specific regulatory tyrosine and threonine sites. We have recently found that activation of p38alpha MAPK can be carried out not only by its upstream MAPK kinases (MKKs) but also by p38alpha autophosphorylation. p38alpha autoactivation requires an interaction of p38alpha with TAB1 (transforming growth factor-beta-activated protein kinase 1-binding protein 1). The autoactivation mechanism of p38alpha has been found to be important in cellular responses to a number of physiologically relevant stimuli. Here, we report the characterization of a splicing variant of TAB1, TAB1beta. TAB1 and TAB1beta share the first 10 exons. The 11th and 12th exons of TAB1 were spliced out in TAB1beta, and an extra exon, termed exon beta, downstream of exons 11 and 12 in the genome was used as the last exon in TAB1beta. The mRNA of TAB1beta was expressed in all cell lines examined. The TAB1beta mRNA encodes a protein with an identical sequence to TAB1 except the C-terminal 69 amino acids were replaced with an unrelated 27-amino acid sequence. Similar to TAB1, TAB1beta interacts with p38alpha but not other MAPKs and stimulates p38alpha autoactivation. Different from TAB1, TAB1beta does not bind or activate TAK1. Inhibition of TAB1beta expression with RNA interference in MDA231 breast cancer cells resulted in the reduction of basal activity of p38alpha and invasiveness of MDA231 cells, suggesting that TAB1beta is involved in regulating p38alpha activity in physiological conditions.