PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
批准号:
6181074
负责人:
Jianxun LI
金额:
$17.86万
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:
1996-08-01 至 2001-07-31
关键词:
alveolar macrophages binding proteins biological signal transduction cell adhesion molecules enzyme substrate enzyme substrate complex integrins leukocyte adhesion molecules molecular cloning mutant paxillin phagocytosis phosphorylation protein kinase C protein purification protein structure function tissue /cell culture
中文摘要
本申请旨在研究β 2-整联蛋白活化的调节,
特别是蛋白激酶C(PKC)介导的β 2-整联蛋白激活。
在β 2整合素依赖的信号转导通路中,
PKC的活化是整联蛋白活化所必需的。 数据
MacMARCKS是白细胞中主要的PKC底物,
在β 2整合素依赖性信号转导中的重要作用
途径。 因此,本提案的重点是MacMARCKS如何监管
β 2-整合素家族的激活。
这一提议将检验MacMARCKS是一个
转导PKC介导的磷酸化信号以激活
β 2-整合素依赖性信号转导途径。 的
MacMARCKS的磷酸化消除和假磷酸化突变体
以及它们对β 2-整合素依赖性
将确定细胞功能。
初步研究表明,MacMARCKS在体内与
桩蛋白,一种粘着斑蛋白,是β 2-整联蛋白的一部分,
依赖的信号转导途径。 MacMARCKS-桩蛋白
将描述这种关联的特征,并且PKC介导的MacMARCKS
对桩蛋白酪氨酸磷酸化的磷酸化作用将是
考察 将检验MacMARCKS-桩蛋白
结合是β 2-整合素依赖性的调节的一部分,
途径。
最后,克隆的新的47 kDa MacMARCKS结合蛋白将在
表征了 MacMARCKS与47 kDa蛋白的相互作用
也将受到审查,并将调查其监管情况。 的
拟议的工作将研究47 kDa蛋白在
整合MacMARCKS和其他粘着斑蛋白,包括β 2-
整合素本身,进入β 2-整合素依赖的信号转导
途径。 拟议的研究将导致开发新的
控制白细胞活化和限制癌细胞的策略
通过调节它们的整合素亲合力来转移。
英文摘要
This application is to study the regulation of beta2-integrin activation,
specifically protein kinase C (PKC)-mediated beta2-integrin activation.
In the beta2-integrin-dependent signal transduction pathways, the
activation of PKC is required for the activation of integrin. Data
suggested that MacMARCKS, a major PKC substrate in leukocytes, plays an
essential role in the beta2-integrin-dependent signal transduction
pathways. Thus, this proposal is focused on how MacMARCKS regulates the
activation of the beta2-integrin family.
This proposal will test the hypothesis that MacMARCKS is one of the
molecules which transduces PKC-mediated phosphorylation signal to activate
beta2-integrin-dependent signal transduction pathways. The
phosphorylation-abrogated and pseudo-phosphorylated mutants of MacMARCKS
will be generated and their effects on the beta2-integrin-dependent
cellular functions will be determined.
Preliminary studies suggested that MacMARCKS associates in vivo with
paxillin, a focal adhesion protein that is part of the beta2-integrin-
dependent signal transduction pathways. The MacMARCKS-paxillin
association will be characterized and the effect of PKC-mediated MacMARCKS
phosphorylation on the tyrosine phosphorylation of paxillin will be
examined. The hypothesis will be tested that MacMARCKS-paxillin
association is part of the regulation of the beta2-integrin-dependent
pathways.
Finally, the cloned novel 47 kDa MacMARCKS binding protein will be
characterized. The interaction between MacMARCKS and the 47 kDa protein
will also be examined and their regulation will be investigated. The
proposed work will investigate the potential role of the 47 kDa protein in
integrating MacMARCKS and other focal adhesion proteins, including beta2-
integrin itself, into the beta2-integrin-dependent signal transduction
pathways. The proposed studies would lead to the development of new
strategies to control the leukocyte activation and to limit cancer cell
metastasis by modulating their integrin avidity.
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Protein Kinase C-mediated Integrin Activation
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批准号:6525729
-
项目类别:
-
资助金额:$23.38万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
Protein Kinase C-mediated Integrin Activation
-
批准号:6778181
-
项目类别:
-
资助金额:$23.38万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
-
批准号:2194052
-
项目类别:
-
资助金额:$15.35万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
-
批准号:6019192
-
项目类别:
-
资助金额:$17.39万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
Protein Kinase C-mediated Integrin Activation
-
批准号:6652013
-
项目类别:
-
资助金额:$23.18万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
-
批准号:2750112
-
项目类别:
-
资助金额:$16.69万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
-
批准号:2686306
-
项目类别:
-
资助金额:$12.48万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
PROTEIN KINASE C--MEDIATED INTEGRIN ACTIVATION
-
批准号:2459706
-
项目类别:
-
资助金额:$3.64万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
Protein Kinase C-mediated Integrin Activation
-
批准号:6370409
-
项目类别:
-
资助金额:$19.48万
-
财政年份:1996
-
负责人:Jianxun LI
-
依托单位:
海外基金