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2
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3
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4
Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase.c-Abl蛋白酪氨酸激酶对雷帕霉素及其FKBP靶点1/哺乳动物雷帕霉素靶点以及帽依赖性翻译起始的调控。
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本文引用的文献

1
Mammalian TOR controls one of two kinase pathways acting upon nPKCdelta and nPKCepsilon.哺乳动物雷帕霉素靶蛋白（mTOR）控制着作用于非典型蛋白激酶Cδ（nPKCδ）和非典型蛋白激酶Cε（nPKCε）的两条激酶途径之一。
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2
Dissociation of the eukaryotic initiation factor-4E/4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinase.真核生物起始因子-4E/4E-BP1复合物的解离涉及一种与mTOR相关的激酶对4E-BP1的磷酸化作用。
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Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism.4E-BP1磷酸化的调控：一种新型的两步机制。
Genes Dev. 1999 Jun 1;13(11):1422-37. doi: 10.1101/gad.13.11.1422.
4
Intracellular signalling: PDK1--a kinase at the hub of things.细胞内信号传导：PDK1——处于关键位置的一种激酶。
Curr Biol. 1999 Feb 11;9(3):R93-6. doi: 10.1016/s0960-9822(99)80058-x.
5
Functional role for protein kinase Cbeta as a regulator of stress-activated protein kinase activation and monocytic differentiation of myeloid leukemia cells.蛋白激酶Cβ作为应激激活蛋白激酶激活和髓系白血病细胞单核细胞分化调节因子的功能作用。
Mol Cell Biol. 1999 Jan;19(1):461-70. doi: 10.1128/MCB.19.1.461.
6
Inactivation of DNA-dependent protein kinase by protein kinase Cdelta: implications for apoptosis.蛋白激酶Cδ使DNA依赖性蛋白激酶失活：对细胞凋亡的影响。
Mol Cell Biol. 1998 Nov;18(11):6719-28. doi: 10.1128/MCB.18.11.6719.
7
Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase.Lyn酪氨酸激酶对DNA依赖性蛋白激酶的调控。
J Biol Chem. 1998 Oct 2;273(40):25654-8. doi: 10.1074/jbc.273.40.25654.
8
Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1.蛋白激酶C同工型由磷酸肌醇3激酶通过蛋白激酶PDK1控制。
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9
Translocation of PKC delta by insulin in a rat hepatoma cell line.胰岛素在大鼠肝癌细胞系中对蛋白激酶Cδ的易位作用。
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10
Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway.由蛋白激酶B信号通路介导的胰岛素刺激雷帕霉素哺乳动物靶标磷酸化和激活的证据。
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RAFT1/FRAP/mTOR与蛋白激酶cdelta在帽依赖性翻译起始调控中的功能相互作用。

Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation.

作者信息

Kumar V, Pandey P, Sabatini D, Kumar M, Majumder P K, Bharti A, Carmichael G, Kufe D, Kharbanda S

机构信息

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

出版信息

EMBO J. 2000 Mar 1;19(5):1087-97. doi: 10.1093/emboj/19.5.1087.

DOI:10.1093/emboj/19.5.1087
PMID:10698949
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC305647/
Abstract

Hormones and growth factors induce protein translation in part by phosphorylation of the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). The rapamycin and FK506-binding protein (FKBP)-target 1 (RAFT1, also known as FRAP) is a mammalian homolog of the Saccharomyces cerevisiae target of rapamycin proteins (mTOR) that regulates 4E-BP1. However, the molecular mechanisms involved in growth factor-initiated phosphorylation of 4E-BP1 are not well understood. Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1. PKCdelta-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation. Moreover, a dominant-negative mutant of PKCdelta inhibits serum-induced phosphorylation of 4E-BP1. These findings demonstrate that PKCdelta associates with RAFT1 and thereby regulates phosphorylation of 4E-BP1 and cap-dependent initiation of protein translation.

摘要

激素和生长因子部分通过真核起始因子4E（eIF4E）结合蛋白1（4E-BP1）的磷酸化来诱导蛋白质翻译。雷帕霉素和FK506结合蛋白（FKBP）靶向蛋白1（RAFT1，也称为FRAP）是酿酒酵母雷帕霉素靶蛋白（mTOR）的哺乳动物同源物，可调节4E-BP1。然而，生长因子引发的4E-BP1磷酸化所涉及的分子机制尚未完全清楚。在此我们证明蛋白激酶Cδ（PKCδ）与RAFT1相互作用，并且PKCδ是4E-BP1磷酸化和失活所必需的。PKCδ介导的4E-BP1磷酸化对渥曼青霉素耐药，但对雷帕霉素敏感。如血清所示，PKCδ介导的4E-BP1磷酸化抑制4E-BP1与eIF4E之间的相互作用，并刺激帽依赖性翻译。此外，PKCδ的显性负性突变体抑制血清诱导的4E-BP1磷酸化。这些发现表明PKCδ与RAFT1相互作用，从而调节4E-BP1的磷酸化和帽依赖性蛋白质翻译起始。