排序方式: 共有16条查询结果,搜索用时 15 毫秒
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Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)
Acosta YY Zafra MP Ojeda G Bernardone IS Dianzani U Portolés P Rojo JM 《Cellular and molecular life sciences : CMLS》2011,68(18):3065-3079
To better understand T lymphocyte costimulation by inducible costimulator (ICOS; H4; CD278), we analyzed proteins binding
to ICOS peptides phosphorylated at the Y191MFM motif. Phosphorylated ICOS binds class IA phosphatidyl inositol 3-kinase (PI3-K) p85α, p50-55α and p85β regulatory subunits
and p110α, p110δ and p110β catalytic subunits. Intriguingly, T cells expressed high levels of both p110α or p110δ catalytic
subunits, yet ICOS peptides, cell surface ICOS or PI3-kinase class IA regulatory subunits preferentially coprecipitated p110α
catalytic subunits. Silencing p110α or p110δ partially inhibited Akt/PKB activation induced by anti-CD3 plus anti-ICOS antibodies.
However, silencing p110α enhanced and silencing p110δ inhibited Erk activation. Both p110α- and p110δ-specific inhibitors
blocked cytokine secretion induced by TCR/CD3 activation with or without ICOS costimulus, but only p110α inhibitors blocked
ICOS-induced cell elongation. Thus, p110α and p110δ are essential to optimal T cell activation, but their abundance and activity
differentially tune up distinct ICOS signaling pathways. 相似文献
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FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation 总被引:1,自引:0,他引:1
Meloni I Muscettola M Raynaud M Longo I Bruttini M Moizard MP Gomot M Chelly J des Portes V Fryns JP Ropers HH Magi B Bellan C Volpi N Yntema HG Lewis SE Schaffer JE Renieri A 《Nature genetics》2002,30(4):436-440
X-linked mental retardation (XLMR) is an inherited condition that causes failure to develop cognitive abilities, owing to mutations in a gene on the X chromosome. The latest XLMR update lists up to 136 conditions leading to 'syndromic', or 'specific', mental retardation (MRXS) and 66 entries leading to 'nonspecific' mental retardation (MRX). For 9 of the 66 MRX entries, the causative gene has been identified. Our recent discovery of the contiguous gene deletion syndrome ATS-MR (previously known as Alport syndrome, mental retardation, midface hypoplasia, elliptocytosis, OMIM #300194), characterized by Alport syndrome (ATS) and mental retardation (MR), indicated Xq22.3 as a region containing one mental retardation gene. Comparing the extent of deletion between individuals with ATS-MR and individuals with ATS alone allowed us to define a critical region for mental retardation of approximately 380 kb, containing four genes. Here we report the identification of two point mutations, one missense and one splice-site change, in the gene FACL4 in two families with nonspecific mental retardation. Analysis of enzymatic activity in lymphoblastoid cell lines from affected individuals of both families revealed low levels compared with normal cells, indicating that both mutations are null mutations. All carrier females with either point mutations or genomic deletions in FACL4 showed a completely skewed X-inactivation, suggesting that the gene influences survival advantage. FACL4 is the first gene shown to be involved in nonspecific mental retardation and fatty-acid metabolism. 相似文献
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Tootle TL Silver SJ Davies EL Newman V Latek RR Mills IA Selengut JD Parlikar BE Rebay I 《Nature》2003,426(6964):299-302