Molecular Mechanisms of Human Disease Mediated by Oncogenic and Primary Immunodeficiency Mutations in Class IA Phosphoinositide 3-Kinases.
Molecular Mechanisms of Human Disease Mediated by Oncogenic and Primary Immunodeficiency Mutations in Class IA Phosphoinositide 3-Kinases.
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DOI：
10.3389/fimmu.2018.00575
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发表时间：
2018
影响因子：
7.3
通讯作者：
Burke JE
中科院分区：
文献类型：
--
作者：
Dornan GL;Burke JE
信号脂质磷脂酰肌醇3，4，5，三磷酸（PIP 3）是许多重要细胞过程（包括生长、存活和代谢）的必需介质。PIP 3通过I类磷酸肌醇3-激酶（PI 3 K）的作用产生，并且它们的活性通过与调节蛋白和活化刺激的相互作用而受到严格控制。IA类PI 3 K由三种不同的p110催化亚基（p110α、p110β和p110δ）组成，由于细胞表面受体下游的表达和接合的差异，它们在特定组织中发挥不同的作用。PI 3 K调节的破坏是许多人类疾病的常见驱动因素。编码IA类PI 3 K的p110α催化亚基的PIK 3CA基因中的激活突变在几种癌症类型中经常发生突变，并且已在原发性免疫缺陷患者中鉴定出编码p110δ催化亚基的PIK 3CD基因中的突变。所有IA类p110亚基与p85调节亚基相互作用，并且在癌症和原发性免疫缺陷中已经鉴定出不同p85调节亚基中的突变/缺失。本文综述了p85调节亚基对IA类PI 3 K催化活性的调节作用，以及PI 3 K催化亚基PIK 3CA、PIK 3CD（p110α、p110δ）和调节亚基PIK 3R 1（p85α）的激活突变如何介导PI 3 K活化和人类疾病的分子基础。
The signaling lipid phosphatidylinositol 3,4,5, trisphosphate (PIP3) is an essential mediator of many vital cellular processes, including growth, survival, and metabolism. PIP3 is generated through the action of the class I phosphoinositide 3-kinases (PI3K), and their activity is tightly controlled through interactions with regulatory proteins and activating stimuli. The class IA PI3Ks are composed of three distinct p110 catalytic subunits (p110α, p110β, and p110δ), and they play different roles in specific tissues due to disparities in both expression and engagement downstream of cell-surface receptors. Disruption of PI3K regulation is a frequent driver of numerous human diseases. Activating mutations in the PIK3CA gene encoding the p110α catalytic subunit of class IA PI3K are frequently mutated in several cancer types, and mutations in the PIK3CD gene encoding the p110δ catalytic subunit have been identified in primary immunodeficiency patients. All class IA p110 subunits interact with p85 regulatory subunits, and mutations/deletions in different p85 regulatory subunits have been identified in both cancer and primary immunodeficiencies. In this review, we will summarize our current understanding for the molecular basis of how class IA PI3K catalytic activity is regulated by p85 regulatory subunits, and how activating mutations in the PI3K catalytic subunits PIK3CA and PIK3CD (p110α, p110δ) and regulatory subunits PIK3R1 (p85α) mediate PI3K activation and human disease.
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影响因子：
--
作者：
Burke, John E;Williams, Roger L
通讯作者：
Williams, Roger L
DOI：
10.1016/j.jaci.2016.06.021
发表时间：
2017-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Coulter TI;Chandra A;Bacon CM;Babar J;Curtis J;Screaton N;Goodlad JR;Farmer G;Steele CL;Leahy TR;Doffinger R;Baxendale H;Bernatoniene J;Edgar JD;Longhurst HJ;Ehl S;Speckmann C;Grimbacher B;Sediva A;Milota T;Faust SN;Williams AP;Hayman G;Kucuk ZY;Hague R;French P;Brooker R;Forsyth P;Herriot R;Cancrini C;Palma P;Ariganello P;Conlon N;Feighery C;Gavin PJ;Jones A;Imai K;Ibrahim MA;Markelj G;Abinun M;Rieux-Laucat F;Latour S;Pellier I;Fischer A;Touzot F;Casanova JL;Durandy A;Burns SO;Savic S;Kumararatne DS;Moshous D;Kracker S;Vanhaesebroeck B;Okkenhaug K;Picard C;Nejentsev S;Condliffe AM;Cant AJ
通讯作者：
Cant AJ
影响因子：
64.5
作者：
Fritsch R;de Krijger I;Fritsch K;George R;Reason B;Kumar MS;Diefenbacher M;Stamp G;Downward J
通讯作者：
Downward J
通过p85α单体二聚体平衡对PI3K途径进行调节。
影响因子：
7.7
作者：
Cheung LW;Walkiewicz KW;Besong TM;Guo H;Hawke DH;Arold ST;Mills GB
通讯作者：
Mills GB
DOI：
10.1126/science.1243292
发表时间：
2013-11-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Angulo I;Vadas O;Garçon F;Banham-Hall E;Plagnol V;Leahy TR;Baxendale H;Coulter T;Curtis J;Wu C;Blake-Palmer K;Perisic O;Smyth D;Maes M;Fiddler C;Juss J;Cilliers D;Markelj G;Chandra A;Farmer G;Kielkowska A;Clark J;Kracker S;Debré M;Picard C;Pellier I;Jabado N;Morris JA;Barcenas-Morales G;Fischer A;Stephens L;Hawkins P;Barrett JC;Abinun M;Clatworthy M;Durandy A;Doffinger R;Chilvers ER;Cant AJ;Kumararatne D;Okkenhaug K;Williams RL;Condliffe A;Nejentsev S
通讯作者：
Nejentsev S