Basal phosphorylation of the PEST domain in the I(kappa)B(beta) regulates its functional interaction with the c-rel proto-oncogene product.
Basal phosphorylation of the PEST domain in the I(kappa)B(beta) regulates its functional interaction with the c-rel proto-oncogene product.
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I(kappa)B(beta) 中 PEST 结构域的基础磷酸化调节其与 c-rel 原癌基因产物的功能相互作用。
DOI：
10.1128/mcb.16.11.5974
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发表时间：
1996
影响因子：
5.3
通讯作者：
Ballard,DW
中科院分区：
文献类型：
--
作者：
Chu,ZL;McKinsey,TA;Liu,L;Qi,X;Ballard,DW
c-relproto癌基因（c-Rel）的产物属于NF-κB/Rel多肽家族，并参与细胞增殖和免疫功能的转录控制。在人T淋巴细胞中，c-Rel通过组成型磷酸化抑制剂（包括IκBα和IκBβ）被隔离在细胞质室中。对细菌表达形式的这些抑制蛋白的研究表明，未磷酸化的IκBα而不是IκBβ与c-Rel组装并抑制其DNA结合活性。此外，来自哺乳动物细胞的潜伏性IκBβ-c-Rel复合物对磷酸酶处理敏感，而IκBα-c-Rel复合物具有抗性。我们已经在未受刺激的T细胞中发现了一种组成蛋白激酶，它与体外的i - κ b β相关并使其磷酸化。这种κ b β相关激酶（BAK）的底物特异性、电泳迁移率和抗原性表明它与酪蛋白激酶II （CKII）相同，后者是一种介导κ b α基础磷酸化的酶。通过BAK或CKII磷酸化重组IκBβ，可以恢复该抑制剂对抗c-Rel DNA结合活性的能力。肽定位和突变分析将IκBβ的大部分基础磷酸化位点定位在c端PEST结构域，该结构域包含两个ckii介导的磷酸化基团转移的潜在受体（Ser-313和Ser-315）。在Ser-313和Ser-315全长抑制剂中引入点突变导致IκBβ磷酸化显著降低，并严重损害其体内c-Rel抑制功能。综上所述，这些发现强烈表明，在一致的CKII位点上，ikb - β的PEST结构域的基础磷酸化是有效形成潜伏的ikb - β - c- rel复合物所必需的。
The product of the c-relproto-oncogene (c-Rel) belongs to the NF-κB/Rel family of polypeptides and has been implicated in the transcriptional control of cell proliferation and immune function. In human T lymphocytes, c-Rel is sequestered in the cytoplasmic compartment by constitutively phosphorylated inhibitors, including IκBα and IκBβ. Studies with bacterially expressed forms of these inhibitory proteins revealed that unphosphorylated IκBα but not IκBβ assembles with c-Rel and inhibits its DNA binding activity. Furthermore, latent IκBβ–c-Rel complexes derived from mammalian cells were sensitive to phosphatase treatment, whereas IκBα–c-Rel complexes were resistant. We have identified a constitutive protein kinase in unstimulated T cells that associates with and phosphorylates IκBβ in vitro. The substrate specificity, electrophoretic mobility, and antigenic properties of this IκBβ-associated kinase (BAK) suggest identity with casein kinase II (CKII), an enzyme known to mediate basal phosphorylation of IκBα. Phosphorylation of recombinant IκBβ by either BAK or CKII restored the capacity of this inhibitor to antagonize the DNA binding activity of c-Rel. Peptide mapping and mutational analyses localized the bulk of the basal phosphorylation sites in IκBβ to the C-terminal PEST domain, which contains two potential acceptors for CKII-mediated phosphoryl group transfer (Ser-313 and Ser-315). Point mutations introduced into the full-length inhibitor at Ser-313 and Ser-315 led to a significant reduction in the phosphorylation of IκBβ and severely impaired its c-Rel inhibitory function in vivo. Taken together, these findings strongly suggest that basal phosphorylation of the PEST domain of IκBβ at consensus CKII sites is required for the efficient formation of latent IκBβ–c-Rel complexes.
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DOI：
10.1016/s0021-9258(18)48058-1
发表时间：
1987-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
E. Kuenzel;J. Mulligan;J. Sommercorn;E. Krebs
通讯作者：
E. Kuenzel;J. Mulligan;J. Sommercorn;E. Krebs
影响因子：
56.9
作者：
ROGERS, S;WELLS, R;RECHSTEINER, M
通讯作者：
RECHSTEINER, M
DOI：
--
发表时间：
1995
期刊：
--
影响因子：
--
作者：
J. Brockman;D. Scherer;T. McKinsey;S. M. Hall;X. Qi;Wha-Young Lee;Anddean W. Ballard
通讯作者：
J. Brockman;D. Scherer;T. McKinsey;S. M. Hall;X. Qi;Wha-Young Lee;Anddean W. Ballard
未磷酸化的新合成 I (cid:107) B (cid:98) 在 NF- (cid:107) B 持续激活中的作用
DOI：
--
发表时间：
1996
期刊：
影响因子：
--
作者：
H. Suyang;R. Phillips;I. Douglas;Sankar Ghosh
通讯作者：
Sankar Ghosh
CD28 共刺激人 T 淋巴细胞 a 中转录因子 c-Rel 和 NF-kB 增强核易位的机制
影响因子：
5.2
作者：
J. Lai;G. Horvath;Yongqin Li;T. Tan
通讯作者：
T. Tan