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
这一应用是为了研究β2整合素激活的调节,
尤其是蛋白激酶C(PKC)介导的β2整合素活化。
在β2整合素依赖的信号转导通路中,
整合素的激活需要PKC的激活。数据
提示,白细胞中主要的PKC底物MacMARCKS在
β2整合素依赖的信号转导中的重要作用
小路。因此,这项建议集中在MacMARCKS如何监管
β2整合素家族的激活。
这一提议将检验麦克马克斯是
转导PKC介导的磷酸化信号以激活的分子
β2-整合素依赖的信号转导通路。这个
MacMARCKS的磷酸化缺失和假磷酸化突变体
及其对β2整合素依赖性的影响
细胞功能将被确定。
初步研究表明,MacMARCKS在体内与
是一种粘着斑蛋白,是β2整合素的一部分。
依赖的信号转导通路。MacMARCKS-帕克西林
联合将表征和PKC介导的MacMARCKS的作用
巴西林酪氨酸磷酸化的磷酸化将是
检查过了。这一假设将得到检验,即麦克马科斯-帕西林
结合是β2整合素依赖的调节的一部分
小路。
最后,克隆的新型47 kDa MacMARCKS结合蛋白将被
特色化的。MacMARCKS与47 kDa蛋白的相互作用
还将对其进行审查,并对其监管进行调查。这个
拟议的工作将调查47 kDa蛋白在
整合MacMARCKS和其他焦点黏附蛋白,包括Beta2-
整合素本身,进入β2整合素依赖的信号转导
小路。拟议的研究将导致发展新的
控制白细胞活化和限制癌细胞的策略
通过调节其整合素亲和力进行转移。
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
-
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
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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
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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