Characterization of signaling function and expression of HLA class I molecules in medulloblastoma.
Characterization of signaling function and expression of HLA class I molecules in medulloblastoma.
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DOI：
10.1007/s11060-010-0378-3
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发表时间：
2011-06
影响因子：
3.9
通讯作者：
Vukmanovic S
中科院分区：
文献类型：
--
作者：
Smith C;Santi M;Rushing EJ;Cornelison R;MacDonald TJ;Vukmanovic S
虽然已知在免疫系统中的重要功能，但越来越多地认为MHC I类分子在修饰信号转导中具有替代作用。在髓母细胞瘤中，HLA I类分子与预后不良相关，并且在与结合不完全组装复合物（所谓的开放构象异构体）的配体结合时可以诱导ERK 1/2活化。我们在此证明，在缺乏内源性合成β 2 m的情况下，成神经管细胞瘤中ERK 1/2的激活也可能发生，正式排除了封闭的HLA类构象的参与。此外，一些实验观察表明，HLA I类表达的异质性可能是转化前原始细胞状态的反映，而不是基于免疫选择HLA缺失突变体的结果。这些结果有助于我们理解HLA I类在髓母细胞瘤和一般癌症病理学中的免疫系统独立作用。
Although known for the important function in the immune system, MHC class I molecules are increasingly ascribed an alternative role in modifying signal transduction. In medulloblastoma, HLA class I molecules are associated with poor prognosis, and can induce ERK1/2 activation upon engagement with ligands that bind to incompletely assembled complexes (so called open conformers). We here demonstrate that ERK1/2 activation in medulloblastoma can occur in the absence of endogenously synthesized β2m, formally excluding involvement of closed HLA class conformation. In addition, several experimental observations suggest that heterogeneity of HLA class I expression may be a reflection of the status of original cells before transformation, rather than a consequence of immune-based selection of HLA-loss mutants. These results contribute to our understanding of an immune system-independent role of HLA class I in the pathology of medulloblastoma, and cancer in general.
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影响因子：
5.4
作者：
JEFFERIES, WA;MACPHERSON, GG
通讯作者：
MACPHERSON, GG
影响因子：
64.8
作者：
CRAIR, MC;MALENKA, RC
通讯作者：
MALENKA, RC
影响因子：
56.9
作者：
Huh, GS;Boulanger, LM;Shatz, CJ
通讯作者：
Shatz, CJ
影响因子：
4.3
作者：
DEMARIA, S;SCHWAB, R;BUSHKIN, Y
通讯作者：
BUSHKIN, Y
DOI：
10.1073/pnas.81.20.6476
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LAMPSON, LA;FISHER, CA
通讯作者：
FISHER, CA