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本文引用的文献

1
Novel Src homology 3 domain-binding motifs identified from proteomic screen of a Pro-rich region.从富含脯氨酸区域的蛋白质组学筛选中鉴定出的新型Src同源3结构域结合基序。
Mol Cell Proteomics. 2005 Aug;4(8):1155-66. doi: 10.1074/mcp.M500108-MCP200. Epub 2005 May 31.
2
T cell receptor-induced activation of phospholipase C-gamma1 depends on a sequence-independent function of the P-I region of SLP-76.T细胞受体诱导的磷脂酶C-γ1激活取决于SLP-76的P-I区域的序列非依赖性功能。
J Biol Chem. 2005 Mar 4;280(9):8364-70. doi: 10.1074/jbc.M409437200. Epub 2004 Dec 28.
3
Ca2+/calcineurin signalling in cells of the immune system.免疫系统细胞中的钙离子/钙调神经磷酸酶信号传导
Biochem Biophys Res Commun. 2003 Nov 28;311(4):1117-32. doi: 10.1016/j.bbrc.2003.09.174.
4
Differential role of SLP-76 domains in T cell development and function.SLP-76结构域在T细胞发育和功能中的差异作用。
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):884-9. doi: 10.1073/pnas.022619199. Epub 2002 Jan 15.
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Differential requirement for SLP-76 domains in T cell development and function.SLP-76结构域在T细胞发育和功能中的差异需求。
Immunity. 2001 Dec;15(6):1011-26. doi: 10.1016/s1074-7613(01)00253-9.
6
Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.鉴定T细胞受体介导的磷脂酶C-γ1（PLC-γ1）激活和活化T细胞核因子（NFAT）所需的SLP-76中磷脂酶C-γ1（PLC-γ1）Src同源3（SH3）结构域结合位点。
Mol Cell Biol. 2001 Jul;21(13):4208-18. doi: 10.1128/MCB.21.13.4208-4218.2001.
7
RasGRP links T-cell receptor signaling to Ras.RasGRP将T细胞受体信号传导与Ras相连。
Blood. 2000 May 15;95(10):3199-203.
8
HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1.HPK1 被淋巴细胞抗原受体激活，并对 AP-1 进行负调控。
Immunity. 2000 Apr;12(4):399-408. doi: 10.1016/s1074-7613(00)80192-2.
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Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade.整合Itk与T细胞受体启动的信号级联反应的生化相互作用。
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Phospholipase C-gamma as a signal-transducing element.磷脂酶C-γ作为一种信号转导元件。
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Gads结合位点上游的SLP-76中一段10个氨基酸长的序列对T细胞发育和功能至关重要。

A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function.

作者信息

Kumar Lalit, Feske Stefan, Rao Anjana, Geha Raif S

机构信息

Division of Immunology, Children's Hospital, CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19063-8. doi: 10.1073/pnas.0509176102. Epub 2005 Dec 14.

DOI:10.1073/pnas.0509176102
PMID:16354835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1323183/
Abstract

The adapter SLP-76 is essential for T cell development and function. SLP-76 binds to the src homology 3 domain of Lck in vitro. This interaction depends on amino acids 185-194 of SLP-76. To examine the role of the Lck-binding region of SLP-76 in T cell development and function, SLP-76(-/-) mice were reconstituted with an SLP-76 mutant that lacks amino acids 185-194. Double and single positive thymocytes from reconstituted mice were severely reduced in numbers and exhibited impaired positive selection and increased apoptosis. Peripheral T cells were also reduced in numbers, exhibited impaired phospholipase C-gamma1 and Erk phosphorylation, and failed to flux calcium, secrete IL-2, and proliferate in response to T cell antigen receptor ligation. Delayed cutaneous hypersensitivity responses and Ab responses to T cell-dependent antigen were severely impaired. These results indicate that the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function.

摘要

衔接蛋白SLP - 76对T细胞的发育和功能至关重要。SLP - 76在体外可与Lck的src同源3结构域结合。这种相互作用依赖于SLP - 76的第185 - 194位氨基酸。为了研究SLP - 76的Lck结合区域在T细胞发育和功能中的作用，用缺乏第185 - 194位氨基酸的SLP - 76突变体重建SLP - 76(-/-)小鼠。重建小鼠的双阳性和单阳性胸腺细胞数量严重减少，阳性选择受损，凋亡增加。外周T细胞数量也减少，磷脂酶C - γ1和Erk磷酸化受损，对T细胞抗原受体连接无钙流、不分泌IL - 2且不增殖。迟发型皮肤超敏反应和对T细胞依赖性抗原的抗体反应严重受损。这些结果表明，SLP - 76的Lck结合区域对T细胞抗原受体信号传导以及正常T细胞的发育和功能至关重要。