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研究热点：雷帕霉素靶蛋白(mTOR)、磷酸肌醇3激酶(pi3k)信号通路

已有 4713 次阅读 2013-5-8 09:04 |个人分类:热点前沿|系统分类:科研笔记| 蛋白, 通路, 肌醇

利用汤森路透科技集团的基本科学指标库（Essential Science Indicators）2004－2010间的高被引论文及其同被引聚类分析，通过同被引而密切关联的相关论文聚类形成若干个科学研究领域，由此绘制科学文献所反映的科学研究结构地图，讨论科学发展的基本格局。通过研究和揭示科学结构及其演化，为各领域研究提供一种思考问题、发现潜在交叉学科、“热点”领域。

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第一部分：RA 10 的基本信息

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RA ID: 10

RA的名称

雷帕霉素靶蛋白(mTOR)、磷酸肌醇3激酶(pi3k)信号通路与疾病发生的关系

RA的关键词

mammalian target; pik3ca gene; protects against age- and diet-induced obesity while enhancing insulin sensitivity; pathway activation through a pi3k-dependent feedback loop in human cancer; rictor-mtor complex integrity and regulates akt phosphorylation and substrate specificity; mapk pathway activation through a pi3k-dependent feedback loop in human; sin1/mip1 maintains rictor-mtor complex integrity and regulates akt phosphorylation and; s6k1 protects against age- and diet-induced obesity while enhancing insulin; maintains rictor-mtor complex integrity and regulates akt phosphorylation and substrate; ras/erk signaling promotes site-specific ribosomal protein s6 phosphorylation via rsk

包含RF数(Hot RF数)

核心论文数

被引用篇数

总被引次数

平均出版年

9(4)

3792

8792

2006.7

该RA中包含RF的图谱

核糖体蛋白S6激酶磷酸化的调节作用

mTORC1与mTORC2、氨基酸对mTOR的调控机制、mTOR对akt/makp信号通路的调节

RA概述

雷帕霉素（Rapamycin）自20世纪70年代开发出来便经常作为免疫抑制剂用于器官移植，以减缓器官移植手术后的免疫排斥反应，特别是肾移植。雷帕霉素的涂层支架已为成千上万的冠心病患者解决了冠脉支架植入后的再狭窄问题，此外，新近发现雷帕霉素相关产品还是许多癌症治疗的重要靶向药物的选择。雷帕霉素靶蛋白（mTOR）作为细胞内激酶，是高分子量丝氨酸-苏氨酸激酶、磷酸肌醇3-激酶(PI3K)相关激酶(PIKK)的家族成员。近几年的研究发现mTOR传导通路的异常也可以诱发许多疾病。mTOR信号通路在神经疾病和抗衰老、炎症性疾病、纤维化疾病、肺动脉高压等诸多领域研究活跃，具有无限的市场应用前景。而对mTOR进行抑制便成为治疗与该通路密切相关的肿瘤包括肾癌、淋巴瘤、肺癌、肝癌、乳腺癌、神经内分泌癌和胃癌等的靶点所在。

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第二部分：RA 10 包含的9个RF的基本信息

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RF ID: 6247
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
25	1434	3625	2007.5	Yes
RF的关键词	mtor-mediated translational control molecular mechanisms; mtor complex 2 (mtorc2) controls hydrophobic motif phosphorylation; intact mtor signaling complex 2; pras40 regulates mtorc1 kinase activity; mammalian tor complex 2 controls
RF ID: 6714
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
20	987	2012	2007.3	No
RF的关键词	mtor/phosphatidylinositol 3-kinase inhibitor nvp-bez235 lapatinib resistance reversal; vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug; pi 3-kinase p110 beta
RF ID: 8254
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
11	900	2120	2005.5	No
RF的关键词	oncogenic pi3k alpha mutations; phosphatidylinositol 3-kinase mutations identified; human breast cancers; human p110 alpha/p85 alpha complex elucidates; pik3ca mutations correlate
RF ID: 11354
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
5	387	817	2005.0	No
RF的关键词	amino acid mtor/raptor signaling class-3 phosphatidylinosital 30h-kinase mediation; nutrient-regulated lipid kinase required; mammalian target; amino acid sufficiency; p70 s6 kinase
RF ID: 13303
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
3	505	849	2004.0	No
RF的关键词	tsc/rheb/mtor/s6k cassette inappropriate activation induces irs1/2 depletion-insulin resistance-cell survival deficiencies; enhancing insulin sensitivity; insulin resistance; tsc1-2 tumor suppressor controls insulin-p13k signaling
RF ID: 14863
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
3	315	405	2005.6	No
RF的关键词	ras/erk signaling; site-specific ribosomal protein s6 phosphorylation; mitogen-activated protein kinase-dependent s6 kinase pathway; protein synthesis; rapamycin-sensitive 5 ''-terminal oligopyrimidine mrna translation
RF ID: 9782
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
3	395	574	2006.0	Yes
RF的关键词	mtor inhibition induces upstream receptor tyrosine kinase signaling; rapamycin induces feedback activation; akt signaling; rapamycin inhibition; activates akt
RF ID: 7986
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
2	72	120	2008.0	Yes
RF的关键词	erk mapk signaling; hormone-refractory prostate cancer; mapk pathway activation; human cancer; pi3k-dependent feedback loop; preclinical mouse model
RF ID: 12550
核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
2	70	108	2008.0	Yes
RF的关键词	oncogenic cellular transformation; class ipi3k; pi3k/akt pathway; cancer; drug discovery

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第三部分：9个RF的核心论文详细列表

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RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
6247	25	1434	3625	2007.5	Yes
RF的关键词	mtor-mediated translational control molecular mechanisms; mtor complex 2 (mtorc2) controls hydrophobic motif phosphorylation; intact mtor signaling complex 2; pras40 regulates mtorc1 kinase activity; mammalian tor complex 2 controls

论文题目	被引	年份	刊名	第一作者	第一机构、国家
phosphorylation and regulation of akt/pkb by the rictor-mtor complex	1007	2005	SCIENCE	SARBASSOV DD	MIT, USA
rictor, a novel binding partner of mtor, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton	457	2004	CURR BIOL	SARBASSOV DD	MIT, USA
prolonged rapamycin treatment inhibits mtorc2 assembly and akt/pkb	348	2006	MOL CELL	SARBASSOV DD	Whitehead Inst Biomed Res, USA
mammalian tor complex 2 controls the actin cytoskeleton and is rapamycin insensitive	315	2004	NAT CELL BIOL	JACINTO E	Univ Basel, Switzerland
sin1/mip1 maintains rictor-mtor complex integrity and regulates akt phosphorylation and substrate specificity	190	2006	CELL	JACINTO E	Univ Texas, USA
mtor center dot rictor is the ser(473) kinase for akt/protein kinase b in 3t3-l1 adipocytes	174	2005	J BIOL CHEM	HRESKO RC	Washington Univ, USA
ablation in mice of the mtorc components raptor, rictor, or mlst8 reveals that mtorc2 is required for signaling to akt-foxo and pkc alpha but not s6k1	164	2006	DEV CELL	GUERTIN DA	MIT, USA
pras40 is an insulin-regulated inhibitor of the mtorc1 protein kinase	141	2007	MOL CELL	SANCAK Y	MIT, USA
ampk phosphorylation of raptor mediates a metabolic checkpoint	130	2008	MOL CELL	GWINN DM	Salk Inst Biol Studies, USA
insulin signalling to mtor mediated by the akt/pkb substrate pras40	118	2007	NAT CELL BIOL	VANDER HAAR E	Univ Minnesota, USA
the rag gtpases bind raptor and mediate amino acid signaling to mtorc1	114	2008	SCIENCE	SANCAK Y	MIT, USA
msin1 is necessary for akt/pkb phosphorylation, and its isoforms define three distinct mtorc2s	93	2006	CURR BIOL	FRIAS MA	MIT, USA
regulation of torc1 by rag gtpases in nutrient response	66	2008	NAT CELL BIOL	KIM E	Univ Calif San Diego, USA
pras40 regulates mtorc1 kinase activity by functioning as a direct inhibitor of substrate binding	63	2007	J BIOL CHEM	WANG LF	Univ Virginia Hlth Syst, USA
active-site inhibitors of mtor target rapamycin-resistant outputs of mtorc1 and mtorc2	51	2009	PLOS BIOL	FELDMAN ME	Univ Calif San Francisco, USA
mtor complex 2 (mtorc2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (sgk1)	43	2008	BIOCHEM J	GARCIA-MARTINEZ JM	Univ Dundee, Scotland
molecular mechanisms of mtor-mediated translational control	41	2009	NAT REV MOL CELL BIOL	MA XJM	Genentech Inc, USA
mtor complex 2 is required for the development of prostate cancer induced by pten loss in mice	24	2009	CANCER CELL	GUERTIN DA	Whitehead Inst Biomed Res, USA
biochemical, cellular, and in vivo activity of novel atp-competitive and selective inhibitors of the mammalian target of rapamycin	21	2009	CANCER RES	YU K	Wyeth Res, USA
ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mtor)	20	2009	BIOCHEM J	GARCIA-MARTINEZ JM	Univ Dundee, Scotland
torc-specific phosphorylation of mammalian target of rapamycin (mtor): phospho-ser(2481) is a marker for intact mtor signaling complex 2	15	2009	CANCER RES	COPP J	Salk Inst Biol Studies, USA
rictor/torc2 regulates caenorhabditis elegans fat storage, body size, and development through sgk-1	15	2009	PLOS BIOL	JONES KT	Univ Calif San Francisco, USA
the pharmacology of mtor inhibition	7	2009	SCI SIGNAL	GUERTIN DA	Nine Cambridge Ctr, USA
differential requirement of mtor in postmitotic tissues and tumorigenesis	4	2009	SCI SIGNAL	NARDELLA C	Harvard Univ, USA
characterization of the intrinsic and tsc2-gap-regulated gtpase activity of rheb by real-time nmr	4	2009	SCI SIGNAL	MARSHALL CB	Univ Hlth Network, Canada

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
6714	20	987	2012	2007.3	No
RF的关键词	mtor/phosphatidylinositol 3-kinase inhibitor nvp-bez235 lapatinib resistance reversal; vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug; pi 3-kinase p110 beta

论文题目	被引	年份	刊名	第一作者	第一机构、国家
pten activation contributes to tumor inhibition by trastuzumab, and loss of pten predicts trastuzumab resistance in patients	394	2004	CANCER CELL	NAGATA Y	Univ Texas, USA
a pharmacological map of the pi3-k family defines a role for p110 alpha in insulin signaling	253	2006	CELL	KNIGHT ZA	Univ Calif San Francisco, USA
a dual pi3 kinase/mtor inhibitor reveals emergent efficacy in glioma	190	2006	CANCER CELL	FAN QW	Univ Calif San Francisco, USA
a functional genetic approach identifies the pi3k pathway as a major determinant of trastuzumab resistance in breast cancer	155	2007	CANCER CELL	BERNS K	Netherlands Canc Inst, Netherlands
insulin-like growth factor-i receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells	144	2005	CANCER RES	NAHTA R	Univ Texas, USA
pi 3-kinase p110 beta: a new target for antithrombotic therapy	137	2005	NATURE MED	JACKSON SP	Monash Univ, Australia
critical role for the p110 alpha phosphoinositide-3-oh kinase in growth and metabolic regulation	101	2006	NATURE	FOUKAS LC	Ludwig Inst Canc Res, England
identification and characterization of nvp-bez235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity	99	2008	MOL CANCER THER	MAIRA SM	Novartis Pharma AG, Switzerland
pharmacologic characterization of a potent inhibitor of class i phosphatidylinositide 3-kinases	86	2007	CANCER RES	RAYNAUD FI	Inst Canc Res, England
effective use of pi3k and mek inhibitors to treat mutant kras g12d and pik3ca h1047r murine lung cancers	70	2008	NATURE MED	ENGELMAN JA	Beth Israel Hosp, USA
essential roles of pi(3)k-p110 beta in cell growth, metabolism and tumorigenesis	61	2008	NATURE	JIA SD	Dana Farber Canc Inst, USA
a vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, sf1126, with antitumor and antiangiogenic activity	50	2008	CANCER RES	GARLICH JR	Aflac Canc Ctr & Blood Disorders Serv, USA
nvp-bez235, a dual pi3k/mtor inhibitor, prevents pi3k signaling and inhibits the growth of cancer cells with activating pi3k mutations	50	2008	CANCER RES	SERRA V	Vall Hebron Univ Hosp, Spain
the identification of 2-(1h-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (gdc-0941) as a potent, selective, orally bioavailable inhibitor of class ipi3 kinase for the treatment of cancer	50	2008	J MED CHEM	FOLKES AJ	Piramed Pharma, England
angiogenesis selectively requires the p110 alpha isoform of pi3k to control endothelial cell migration	49	2008	NATURE	GRAUPERA M	Canc Res UK London Res Inst, England
the p110 beta isoform of phosphoinositide 3-kinase signals downstream of g protein-coupled receptors and is functionally redundant with p110 gamma	45	2008	PROC NAT ACAD SCI USA	GUILLERMET-GUIBERT J	Queen Mary Univ London, England
phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mtor/phosphatidylinositol 3-kinase inhibitor nvp-bez235	35	2008	CANCER RES	EICHHORN PJA	Vall Hebron Univ Hosp, Spain
mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor px-866 whereas oncogenic ras is a dominant predictor for resistance	16	2009	CANCER RES	IHLE NT	MD Anderson Canc Ctr, USA
akt-independent signaling downstream of oncogenic pik3ca mutations in human cancer	14	2009	CANCER CELL	VASUDEVAN KM	Harvard Univ, USA
breast tumor cells with pi3k mutation or her2 amplification are selectively addicted to akt signaling	13	2008	PLOS ONE	SHE QB	Mem Sloan Kettering Canc Ctr, USA

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
8254	11	900	2120	2005.5	No
RF的关键词	oncogenic pi3k alpha mutations; phosphatidylinositol 3-kinase mutations identified; human breast cancers; human p110 alpha/p85 alpha complex elucidates; pik3ca mutations correlate

论文题目	被引	年份	刊名	第一作者	第一机构、国家
high frequency of mutations of the pik3ca gene in human cancers	687	2004	SCIENCE	SAMUELS Y	Johns Hopkins Univ, USA
mutation of the pik3ca gene in ovarian and breast cancer	245	2004	CANCER RES	CAMPBELL IG	Peter MacCallum Canc Ctr, Australia
phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic	225	2005	PROC NAT ACAD SCI USA	KANG SY	Scripps Res Inst, USA
mutant pik3ca promotes cell growth and invasion of human cancer cells	208	2005	CANCER CELL	SAMUELS Y	Johns Hopkins Univ, USA
pik3ca mutations correlate with hormone receptors, node metastasis, and erbb2, and are mutually exclusive with pten loss in human breast carcinoma	190	2005	CANCER RES	SAAL LH	Columbia Univ Coll Phys & Surg, USA
the pik3ca gene is mutated with high frequency in human breast cancers	161	2004	CANCER BIOL THER	BACHMAN KE	Johns Hopkins Univ, USA
pik3ca gene is frequently mutated in breast carcinomas and hepatocellular carcinomas	146	2005	ONCOGENE	LEE JW	Catholic Univ Korea, South Korea
cancer-specific mutations in pik3ca are oncogenic in vivo	95	2006	PROC NAT ACAD SCI USA	BADER AG	Scripps Res Inst, USA
the structure of a human p110 alpha/p85 alpha complex elucidates the effects of oncogenic pi3k alpha mutations	68	2007	SCIENCE	HUANG CH	Johns Hopkins Kimmel Canc Ctr, USA
mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit	61	2007	SCIENCE	MILED N	MRC, England
helical domain and kinase domain mutations in p110 alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms	34	2008	PROC NAT ACAD SCI USA	ZHAO L	Scripps Res Inst, USA

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
11354	5	387	817	2005.0	No
RF的关键词	amino acid mtor/raptor signaling class-3 phosphatidylinosital 30h-kinase mediation; nutrient-regulated lipid kinase required; mammalian target; amino acid sufficiency; p70 s6 kinase

论文题目	被引	年份	刊名	第一作者	第一机构、国家
amino acids mediate mtor/raptor signaling through activation of class 3 phosphatidylinositol 30h-kinase	217	2005	PROC NAT ACAD SCI USA	NOBUKUNI T	Univ Utrecht, Netherlands
rheb binds and regulates the mtor kinase	198	2005	CURR BIOL	LONG X	Massachusetts Gen Hosp, USA
hvps34 is a nutrient-regulated lipid kinase required for activation of p70 s6 kinase	177	2005	J BIOL CHEM	BYFIELD MP	Albert Einstein Coll Med, USA
the tuberous sclerosis protein tsc2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses	115	2005	J BIOL CHEM	SMITH EM	Univ British Columbia, Canada
rheb binding to mammalian target of rapamycin (mtor) is regulated by amino acid sufficiency	110	2005	J BIOL CHEM	LONG XM	Harvard Univ, USA

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
13303	3	505	849	2004.0	No
RF的关键词	tsc/rheb/mtor/s6k cassette inappropriate activation induces irs1/2 depletion-insulin resistance-cell survival deficiencies; enhancing insulin sensitivity; insulin resistance; tsc1-2 tumor suppressor controls insulin-p13k signaling

论文题目	被引	年份	刊名	第一作者	第一机构、国家
absence of s6k1 protects against age- and diet-induced obesity while enhancing insulin sensitivity	362	2004	NATURE	UM SH	Friedrich Miescher Inst Biomed Res, Switzerland
the tsc1-2 tumor suppressor controls insulin-p13k signaling via regulation of irs proteins	278	2004	J CELL BIOL	HARRINGTON LS	Inst Canc Res, England
inappropriate activation of the tsc/rheb/mtor/s6k cassette induces irs1/2 depletion, insulin resistance, and cell survival deficiencies	209	2004	CURR BIOL	SHAH OJ	Salk Inst Biol Studies, USA

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
14863	3	315	405	2005.6	No
RF的关键词	ras/erk signaling; site-specific ribosomal protein s6 phosphorylation; mitogen-activated protein kinase-dependent s6 kinase pathway; protein synthesis; rapamycin-sensitive 5 ''-terminal oligopyrimidine mrna translation

论文题目	被引	年份	刊名	第一作者	第一机构、国家
s6k1(-/-)/s6k2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5 '-terminal oligopyrimidine mrna translation and reveal a mitogen-activated protein kinase-dependent s6 kinase pathway	226	2004	MOL CELL BIOL	PENDE M	INSERM 584, France
ribosomal protein s6 phosphorylation: from protein synthesis to cell size	118	2006	TRENDS BIOCHEM SCI	RUVINSKY I	Hebrew Univ Jerusalem, Israel
ras/erk signaling promotes site-specific ribosomal protein s6 phosphorylation via rsk and stimulates cap-dependent translation	61	2007	J BIOL CHEM	ROUX PP	Univ Montreal, Canada

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
9782	3	395	574	2006.0	Yes
RF的关键词	mtor inhibition induces upstream receptor tyrosine kinase signaling; rapamycin induces feedback activation; akt signaling; rapamycin inhibition; activates akt

论文题目	被引	年份	刊名	第一作者	第一机构、国家
mtor inhibition induces upstream receptor tyrosine kinase signaling and activates akt	318	2006	CANCER RES	O'REILLY KE	Mem Sloan Kettering Canc Ctr, USA
activation of akt and eif4e survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition	162	2005	CANCER RES	SUN SY	Emory Univ, USA
rapamycin induces feedback activation of akt signaling through an igf-1r-dependent mechanism	94	2007	ONCOGENE	WAN X	NCI, USA

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
7986	2	72	120	2008.0	Yes
RF的关键词	erk mapk signaling; hormone-refractory prostate cancer; mapk pathway activation; human cancer; pi3k-dependent feedback loop; preclinical mouse model

论文题目	被引	年份	刊名	第一作者	第一机构、国家
inhibition of mtorc1 leads to mapk pathway activation through a pi3k-dependent feedback loop in human cancer	77	2008	J CLIN INVEST	CARRACEDO A	77 Ave Louis Pasteur, USA
targeting akt/mtor and erk mapk signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model	43	2008	J CLIN INVEST	KINKADE CW	Columbia Univ, USA

RF ID	核心论文数	被引用篇数	总被引次数	平均出版年	是否为热点
12550	2	70	108	2008.0	Yes
RF的关键词	oncogenic cellular transformation; class ipi3k; pi3k/akt pathway; cancer; drug discovery

论文题目	被引	年份	刊名	第一作者	第一机构、国家
drug discovery approaches targeting the pi3k/akt pathway in cancer	65	2008	ONCOGENE	GARCIA-ECHEVERRIA C	Novartis Inst Biomed Res, Switzerland
class ipi3k in oncogenic cellular transformation	43	2008	ONCOGENE	ZHAO L	Scripps Res Inst, USA

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