CD45 ISOFORMS AND T CELL ACTIVATION
CD45 ISOFORMS AND T CELL ACTIVATION
批准号:
2672359
负责人:
DAVID M ROTHSTEIN
金额:
$20.75万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-09-30 至 2000-08-31
中文摘要
描述(改编自申请人摘要):CD45家族
英文摘要
DESCRIPTION (Adapted from the Applicant's Abstract): The CD45 family of
transmembrane protein tyrosine phosphatases (PTPases) plays a key role in T
cell activation by regulating the activity of critical protein tyrosine
kinases (PTKs) and their phosphorylated substrates. However, the exact
nature of this regulation, and the identity of additional in vivo substrates
remains uncertain. CD45 is composed of multiple isoforms which differ only
in their extracellular domains. These are differentially distributed on
subsets of T cells having distinct functions. It has been proposed that the
CD45 extracellular domains differentially regulate signaling through the
cytoplasmic domain. However, the actual role of the individual isoforms
remains unclear. Such studies have been hampered by the previous inability
to individually express different CD45 isoforms in the same cell line. The
principal investigator has developed a unique model whereby endogenous CD45
expression in the Jurkat human T cell leukemia line has been specifically
blocked by transfection of a CD45-antisense gene. Antisense transfected
cells lacking CD45 were then reconstituted to uniquely express either the
largest or smallest human CD45 isoform. The applicant has found
isoform-specific differences in IL-2 secretion and in the tyrosine
phosphorylation of several key signaling molecules. These findings indicate
preferential regulation of TCR-generated signaling pathways by these two
isoforms. Using this model system, the investigator seeks to extend these
findings and determine the role of CD45 and its isoforms in regulating T
cell activation. In Aim 1, additional Jurkat derivatives, uniquely
expressing the CD45(0) and CD45(ABC) isoforms in the context of a cloned
Ag-specific TCR will be created, to see if the current observations can be
reproduced in an Ag-specific system. Single isoform transfectants will be
compared in experiments designed to determine the role of individual CD45
isoforms in regulating the activity and phosphorylation of PTKs, particular
critical substrates, and IL-2 secretion. In Aim 2, the role of each of the
two cytoplasmic CD45 PTPase domains in activation signaling and substrate
recruitment in vivo will be determined by examining anti-sense transfectants
reconstituted with defined PTPase mutants. In addition, the potential role
of tyrosine phosphorylation of CD45 in signaling will be determined using
specific Tyr to Phe point mutants. To evaluate possible differential
utilization or regulation of these PTPase domains, these mutants will be
expressed in the context of two different CD45 isoforms. In Aim 3, the
function of the remaining three human CD45 isoforms in regulating IL-2
production, PTK activity, and early tyrosine phosphorylation events will be
determined.
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Role of TIM Molecules in Regulatory and Inflammatory B cells in Allo andAutoimmunity
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批准号:9751742
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项目类别:
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资助金额:$187.07万
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财政年份:2018
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负责人:DAVID M ROTHSTEIN
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依托单位:
Administrative Core
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批准号:10455066
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项目类别:
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资助金额:$8.43万
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财政年份:2018
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负责人:DAVID M ROTHSTEIN
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依托单位:
Inflammatory B cells defined by TIM-4 in the Alloimmune response
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批准号:10214481
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项目类别:
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资助金额:$41.58万
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财政年份:2018
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负责人:DAVID M ROTHSTEIN
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依托单位:
Immunoregulation by TLR-activated TIM-1+ ProB Cells in Transplantation
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批准号:10455069
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项目类别:
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资助金额:$43.75万
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财政年份:2018
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负责人:DAVID M ROTHSTEIN
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依托单位:
Role of TIM Molecules in Regulatory and Inflammatory B cells in Allo andAutoimmunity
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批准号:10214475
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项目类别:
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资助金额:$187.07万
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财政年份:2018
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负责人:DAVID M ROTHSTEIN
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依托单位:
Administrative Core
-
批准号:10214476
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项目类别:
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资助金额:$8.43万
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财政年份:2018
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负责人:DAVID M ROTHSTEIN
-
依托单位:
Role of TIM Molecules in Regulatory and Inflammatory B cells in Allo andAutoimmunity
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批准号:10455065
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项目类别:
-
资助金额:$187.07万
-
财政年份:2018
-
负责人:DAVID M ROTHSTEIN
-
依托单位:
Inflammatory B cells defined by TIM-4 in the Alloimmune response
-
批准号:10455071
-
项目类别:
-
资助金额:$41.58万
-
财政年份:2018
-
负责人:DAVID M ROTHSTEIN
-
依托单位:
Immunoregulation by TLR-activated TIM-1+ ProB Cells in Transplantation
-
批准号:10214480
-
项目类别:
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资助金额:$43.75万
-
财政年份:2018
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负责人:DAVID M ROTHSTEIN
-
依托单位:
Inflammatory B Cells Defined by TIM-4 in the Alloimmune Response
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批准号:9542016
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项目类别:
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资助金额:$37.15万
-
财政年份:2017
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负责人:DAVID M ROTHSTEIN
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依托单位:
In Vivo Detection And Mechanisms Of Regulatory B Cell Function In Transplantation
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批准号:9197259
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项目类别:
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资助金额:$37.74万
-
财政年份:2015
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负责人:DAVID M ROTHSTEIN
-
依托单位:
In Vivo Detection And Mechanisms of Regulatory B cell Function in Transplantation
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批准号:10209496
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项目类别:
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资助金额:$46.95万
-
财政年份:2015
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负责人:DAVID M ROTHSTEIN
-
依托单位:
In Vivo Detection And Mechanisms of Regulatory B cell Function in Transplantation
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批准号:10393024
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项目类别:
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资助金额:$47.39万
-
财政年份:2015
-
负责人:DAVID M ROTHSTEIN
-
依托单位:
In Vivo Detection And Mechanisms Of Regulatory B Cell Function In Transplantation
-
批准号:9101948
-
项目类别:
-
资助金额:$37.74万
-
财政年份:2015
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负责人:DAVID M ROTHSTEIN
-
依托单位:
In Vivo Detection And Mechanisms Of Regulatory B Cell Function In Transplantation
-
批准号:8962275
-
项目类别:
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资助金额:$18.87万
-
财政年份:2015
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负责人:DAVID M ROTHSTEIN
-
依托单位:
In Vivo Detection And Mechanisms of Regulatory B cell Function in Transplantation
-
批准号:10598490
-
项目类别:
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资助金额:$47.59万
-
财政年份:2015
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负责人:DAVID M ROTHSTEIN
-
依托单位:
The role of TIM-1 and Regulatory B cells in Allograft Tolerance
-
批准号:8965999
-
项目类别:
-
资助金额:$37.57万
-
财政年份:2011
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负责人:DAVID M ROTHSTEIN
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依托单位:
The role of TIM-1 and Regulatory B cells in Allograft Tolerance
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批准号:8391693
-
项目类别:
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资助金额:$35.32万
-
财政年份:2011
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负责人:DAVID M ROTHSTEIN
-
依托单位:
The role of TIM-1 and Regulatory B cells in Allograft Tolerance
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批准号:8585814
-
项目类别:
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资助金额:$37.57万
-
财政年份:2011
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负责人:DAVID M ROTHSTEIN
-
依托单位:
The role of TIM-1 and Regulatory B cells in Allograft Tolerance
-
批准号:8218396
-
项目类别:
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资助金额:$38.86万
-
财政年份:2011
-
负责人:DAVID M ROTHSTEIN
-
依托单位:
海外基金